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Acta Cryst. (2008). E64, o598    [ doi:10.1107/S1600536808003176 ]

cis-4-(Tosyloxymethyl)cyclohexanecarboxylic acid

D.-H. Jiang, Z.-H. Mao and H. Zheng

Abstract top

The title compound, C15H20O5S, is an intermediate in the synthesis of novel aminocarboxylic acid derivatives. The cyclohexane ring exhibits a chair conformation. In the crystal structure, adjacent molecules form dimers via O-H...O hydrogen bonds.

Comment top

Some aminocarboxylic acid derivatives are used as anti-ulcer agents (Hoshina et al., 1984). To find new anti-ulcer agents, a series of trans/cis-cyclohexanecarboxylic acid derivatives were designed and synthesized.

In this paper, we want to report the synthesis and structure of the title compound, cis-4-(tosyloxymethyl)cyclohexanecarboxylic acid.

The cyclohexane ring exhibits a chair conformation and the cyclohexane C—C bond lengths and C—C—C endocyclic angles are in the range found for similar compounds (van Koningsveld, 1972) (Fig.1). They agree well with those of trans-4-(tosyloxymethyl)cyclohexanecarboxylic acid (Qi et al., 2008).

In the crystal structure, two molecules form centrosymmetric dimers via O—H···O hydrogen bonds (Fig. 2).

Related literature top

For the use of aminocarboxylic acid derivatives as anti-ulcer agents, see: Hoshina et al. (1984). For related structures, see: Qi et al. (2008); van Koningsveld et al. (1972).

Experimental top

cis-4-(Methoxycarboxyl)cyclohexanemethanol (10 mmol), pyridine (11 mmol) and a small amount of 4-dimethylaminopyridine were dissolved in dichloromethane (20 ml), then p-toluenesulfonyl chloride (11 mmol) was added dropwise with vigorous stirring at room temperature. After 8 h the reaction was quenched by addition of water and the organic layer separated was evaporated under vacuum, the solid obtained was hydrolyzed in a mixed solution of methanol and aqueous NaOH (11 mmol) for 4 h at 323 K. The title compound was then obtained by acidification with hydrochloric acid followed by recrystallization from ethyl acetate. Colorless crystals suitable for X-ray analysis were obtained by slow evaporation in ethyl acetate at room temperature.

Refinement top

The H atoms were placed in the calculated positions in the riding model approximation with C—H = 0.93 (aromatic-H) and 0.96 (methyl-H), O—H = 0.82 Å (hydroxyl) and with Uiso(H) = 1.2Ueq(aromatic-C) and 1.5Ueq(methyl-C, hydroxyl). Methyl and hydroxyl H atoms were allowed to rotate around the C—C and C—O axis but not to tilt to best fit the experimental electron density.

Computing details top

Data collection: DIFRAC (Gabe et al., 1993); cell refinement: DIFRAC (Gabe et al., 1993); data reduction: NRCVAX (Gabe et al., 1989); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level.
[Figure 2] Fig. 2. Packing diagram of the title compound.
cis-4-(Tosyloxymethyl)cyclohexanecarboxylic acid top
Crystal data top
C15H20O5SF000 = 664
Mr = 312.37Dx = 1.309 Mg m−3
Monoclinic, P21/cMo Kα radiation
λ = 0.71073 Å
a = 12.545 (4) ÅCell parameters from 43 reflections
b = 10.085 (3) Åθ = 4.4–7.3º
c = 12.654 (6) ŵ = 0.22 mm−1
β = 98.05 (3)ºT = 291 (2) K
V = 1585.1 (10) Å3Block, colourless
Z = 40.45 × 0.40 × 0.38 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.004
Radiation source: fine-focus sealed tubeθmax = 25.5º
Monochromator: graphiteθmin = 1.6º
T = 291(2) Kh = −15→15
ω/2θ scansk = 0→12
Absorption correction: nonel = −6→15
4142 measured reflections3 standard reflections
2931 independent reflections every 250 reflections
1794 reflections with I > 2σ(I) intensity decay: 0.8%
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.044  w = 1/[σ2(Fo2) + (0.0689P)2 + 0.1341P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.130(Δ/σ)max < 0.001
S = 1.03Δρmax = 0.24 e Å−3
2931 reflectionsΔρmin = −0.26 e Å−3
197 parametersExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0109 (15)
Secondary atom site location: difference Fourier map
Crystal data top
C15H20O5SV = 1585.1 (10) Å3
Mr = 312.37Z = 4
Monoclinic, P21/cMo Kα
a = 12.545 (4) ŵ = 0.22 mm−1
b = 10.085 (3) ÅT = 291 (2) K
c = 12.654 (6) Å0.45 × 0.40 × 0.38 mm
β = 98.05 (3)º
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.004
Absorption correction: none3 standard reflections
4142 measured reflections every 250 reflections
2931 independent reflections intensity decay: 0.8%
1794 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.044197 parameters
wR(F2) = 0.130H-atom parameters constrained
S = 1.03Δρmax = 0.24 e Å−3
2931 reflectionsΔρmin = −0.26 e Å−3
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
xyzUiso*/Ueq
S10.88825 (5)1.11227 (6)0.13440 (6)0.0571 (2)
O10.86629 (16)1.13334 (18)0.24047 (15)0.0714 (6)
O20.92693 (13)0.96607 (16)0.12094 (14)0.0587 (5)
O30.96662 (14)1.19132 (18)0.09296 (16)0.0734 (6)
O40.61080 (15)0.4878 (2)0.08885 (17)0.0756 (6)
O50.60020 (17)0.5097 (3)−0.08567 (17)0.0921 (7)
H50.53560.5095−0.08120.138*
C10.6708 (2)1.1419 (3)0.0859 (2)0.0655 (7)
H10.66891.14570.15910.079*
C20.5771 (2)1.1563 (3)0.0140 (3)0.0768 (9)
H20.51221.17060.03990.092*
C30.5778 (2)1.1499 (3)−0.0942 (3)0.0718 (8)
C40.6745 (3)1.1276 (3)−0.1305 (2)0.0744 (8)
H40.67631.1214−0.20350.089*
C50.7684 (2)1.1143 (3)−0.0613 (2)0.0673 (7)
H5A0.83311.1002−0.08760.081*
C60.7667 (2)1.1218 (2)0.0466 (2)0.0517 (6)
C70.4746 (3)1.1693 (4)−0.1705 (3)0.1080 (12)
H7A0.41731.1920−0.13090.162*
H7B0.45691.0887−0.20940.162*
H7C0.48431.2394−0.21960.162*
C80.8744 (2)0.8621 (2)0.1757 (2)0.0574 (7)
H8A0.80050.88700.18020.069*
H8B0.91160.85090.24770.069*
C90.87667 (18)0.7337 (2)0.11476 (18)0.0475 (6)
H90.95160.71400.10650.057*
C100.8351 (2)0.6228 (2)0.1803 (2)0.0537 (6)
H10A0.88000.61700.24900.064*
H10B0.76230.64340.19260.064*
C110.8356 (2)0.4903 (2)0.1233 (2)0.0628 (7)
H11A0.90950.46430.12010.075*
H11B0.80360.42370.16440.075*
C120.7748 (2)0.4936 (3)0.0110 (2)0.0618 (7)
H120.79140.4111−0.02420.074*
C130.8138 (2)0.6083 (3)−0.0531 (2)0.0620 (7)
H13A0.88690.5905−0.06590.074*
H13B0.76870.6138−0.12180.074*
C140.81088 (19)0.7401 (2)0.00422 (18)0.0509 (6)
H14A0.73690.76270.01080.061*
H14B0.83960.8090−0.03730.061*
C150.6550 (2)0.4981 (2)0.0095 (2)0.0608 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0529 (4)0.0520 (4)0.0648 (5)−0.0071 (3)0.0025 (3)−0.0085 (3)
O10.0762 (13)0.0768 (13)0.0589 (12)−0.0026 (10)0.0017 (10)−0.0190 (9)
O20.0526 (10)0.0551 (10)0.0697 (12)−0.0066 (8)0.0133 (9)−0.0022 (8)
O30.0561 (12)0.0641 (11)0.0990 (15)−0.0186 (9)0.0074 (10)0.0001 (10)
O40.0562 (12)0.1058 (16)0.0645 (13)−0.0209 (10)0.0070 (10)−0.0001 (11)
O50.0640 (13)0.139 (2)0.0713 (14)−0.0219 (14)0.0036 (11)0.0193 (13)
C10.0573 (17)0.0739 (18)0.0659 (18)−0.0063 (14)0.0111 (15)−0.0126 (14)
C20.0484 (17)0.091 (2)0.091 (2)−0.0003 (15)0.0110 (16)−0.0210 (18)
C30.0640 (19)0.0699 (18)0.077 (2)−0.0004 (14)−0.0058 (17)−0.0145 (15)
C40.076 (2)0.089 (2)0.0558 (18)0.0038 (17)0.0018 (16)−0.0006 (15)
C50.0593 (17)0.0799 (19)0.0640 (19)0.0029 (14)0.0128 (15)−0.0006 (14)
C60.0525 (15)0.0462 (13)0.0558 (15)−0.0047 (11)0.0055 (12)−0.0056 (11)
C70.077 (2)0.130 (3)0.106 (3)0.012 (2)−0.025 (2)−0.018 (2)
C80.0589 (16)0.0625 (16)0.0506 (15)−0.0092 (12)0.0071 (13)0.0009 (12)
C90.0410 (13)0.0525 (13)0.0482 (14)−0.0033 (11)0.0035 (11)0.0020 (11)
C100.0464 (14)0.0613 (15)0.0517 (14)−0.0021 (12)0.0010 (11)0.0106 (12)
C110.0499 (15)0.0558 (15)0.082 (2)0.0018 (12)0.0072 (14)0.0111 (13)
C120.0616 (17)0.0529 (14)0.0721 (19)−0.0055 (12)0.0138 (14)−0.0088 (12)
C130.0559 (15)0.0810 (18)0.0511 (15)−0.0119 (14)0.0144 (13)−0.0095 (14)
C140.0487 (14)0.0576 (14)0.0466 (14)−0.0070 (11)0.0070 (11)0.0062 (11)
C150.0596 (17)0.0564 (15)0.0647 (19)−0.0165 (13)0.0023 (15)0.0002 (13)
Geometric parameters (Å, °) top
S1—O31.4218 (18)C7—H7C0.9600
S1—O11.423 (2)C8—C91.510 (3)
S1—O21.5688 (18)C8—H8A0.9700
S1—C61.759 (3)C8—H8B0.9700
O2—C81.464 (3)C9—C141.523 (3)
O4—C151.217 (3)C9—C101.526 (3)
O5—C151.306 (3)C9—H90.9800
O5—H50.8200C10—C111.519 (3)
C1—C61.380 (4)C10—H10A0.9700
C1—C21.390 (4)C10—H10B0.9700
C1—H10.9300C11—C121.516 (4)
C2—C31.372 (4)C11—H11A0.9700
C2—H20.9300C11—H11B0.9700
C3—C41.374 (4)C12—C151.501 (4)
C3—C71.515 (4)C12—C131.532 (4)
C4—C51.372 (4)C12—H120.9800
C4—H40.9300C13—C141.517 (3)
C5—C61.371 (4)C13—H13A0.9700
C5—H5A0.9300C13—H13B0.9700
C7—H7A0.9600C14—H14A0.9700
C7—H7B0.9600C14—H14B0.9700
O3—S1—O1119.95 (12)C8—C9—C10108.55 (19)
O3—S1—O2104.28 (11)C14—C9—C10110.34 (18)
O1—S1—O2110.26 (11)C8—C9—H9108.4
O3—S1—C6108.65 (12)C14—C9—H9108.4
O1—S1—C6108.78 (13)C10—C9—H9108.4
O2—S1—C6103.69 (10)C11—C10—C9111.2 (2)
C8—O2—S1117.09 (15)C11—C10—H10A109.4
C15—O5—H5109.5C9—C10—H10A109.4
C6—C1—C2118.7 (3)C11—C10—H10B109.4
C6—C1—H1120.7C9—C10—H10B109.4
C2—C1—H1120.7H10A—C10—H10B108.0
C3—C2—C1121.7 (3)C12—C11—C10113.0 (2)
C3—C2—H2119.2C12—C11—H11A109.0
C1—C2—H2119.2C10—C11—H11A109.0
C2—C3—C4118.1 (3)C12—C11—H11B109.0
C2—C3—C7120.3 (3)C10—C11—H11B109.0
C4—C3—C7121.6 (3)H11A—C11—H11B107.8
C5—C4—C3121.5 (3)C15—C12—C11112.6 (2)
C5—C4—H4119.3C15—C12—C13111.4 (2)
C3—C4—H4119.3C11—C12—C13110.9 (2)
C6—C5—C4119.9 (3)C15—C12—H12107.2
C6—C5—H5A120.1C11—C12—H12107.2
C4—C5—H5A120.1C13—C12—H12107.2
C5—C6—C1120.2 (3)C14—C13—C12112.2 (2)
C5—C6—S1119.5 (2)C14—C13—H13A109.2
C1—C6—S1120.2 (2)C12—C13—H13A109.2
C3—C7—H7A109.5C14—C13—H13B109.2
C3—C7—H7B109.5C12—C13—H13B109.2
H7A—C7—H7B109.5H13A—C13—H13B107.9
C3—C7—H7C109.5C13—C14—C9110.81 (19)
H7A—C7—H7C109.5C13—C14—H14A109.5
H7B—C7—H7C109.5C9—C14—H14A109.5
O2—C8—C9109.29 (19)C13—C14—H14B109.5
O2—C8—H8A109.8C9—C14—H14B109.5
C9—C8—H8A109.8H14A—C14—H14B108.1
O2—C8—H8B109.8O4—C15—O5121.8 (3)
C9—C8—H8B109.8O4—C15—C12123.9 (3)
H8A—C8—H8B108.3O5—C15—C12114.3 (3)
C8—C9—C14112.73 (19)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O5—H5···O4i0.821.832.642 (3)173
Symmetry codes: (i) −x+1, −y+1, −z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O5—H5···O4i0.821.832.642 (3)173
Symmetry codes: (i) −x+1, −y+1, −z.
references
References top

Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565–?.

Gabe, E. J., Le Page, Y., Charland, J.-P., Lee, F. L. & White, P. S. (1989). J. Appl. Cryst. 22, 384–387.

Gabe, E. J., White, P. S. & Enright, G. D. (1993). DIFRAC. American Crystallographic Association, Pittsburgh Meeting, Abstract PA 104.

Hoshina, K., Yamazaki, Y., Takeshita, T. & Naruchi, T. (1984). IUPHAP 9th International Congress of Pharmacology, p. 697. London. Single page article?

Koningsveld, H. van (1972). Acta Cryst. B28, 1189–1195.

Qi, Q.-R., Huang, W.-C. & Zheng, H. (2008). Acta Cryst. E64, o405–?.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.