cis-4-(Tosyl­oxymeth­yl)cyclo­hexa­ne­carboxylic acid

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

doi:10.1107/S1600536808003176

organic compounds

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Volume 64| Part 3| March 2008| Page o598

doi:10.1107/S1600536808003176

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cis-4-(Tosyloxymethyl)cyclohexanecarboxylic acid

De-Hong Jiang,^a Zhi-Hua Mao ^b and Hu Zheng ^a ^*

^aDepartment of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China, and ^bThe Center for Testing and Analysis, Sichuan University, Chengdu 610064, People's Republic of China
^*Correspondence e-mail: wcums416@yahoo.com.cn

(Received 18 January 2008; accepted 29 January 2008; online 15 February 2008)

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.

Related literature

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

Crystal data

C₁₅H₂₀O₅S
M_r = 312.37
Monoclinic, P 2₁ /c
a = 12.545 (4) Å
b = 10.085 (3) Å
c = 12.654 (6) Å
β = 98.05 (3)°
V = 1585.1 (10) Å³
Z = 4
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 291 (2) K
0.45 × 0.40 × 0.38 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: none
4142 measured reflections
2931 independent reflections
1794 reflections with I > 2σ(I)
R_int = 0.004
3 standard reflections every 250 reflections intensity decay: 0.8%

Refinement

R[F² > 2σ(F²)] = 0.044
wR(F²) = 0.130
S = 1.03
2931 reflections
197 parameters
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O5—H5⋯O4ⁱ	0.82	1.83	2.642 (3)	173
Symmetry code: (i) -x+1, -y+1, -z.

Data collection: DIFRAC (Gabe et al., 1993 ); cell refinement: DIFRAC; 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.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808003176/zl2098sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808003176/zl2098Isup2.hkl

checkCIF report

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.

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

	Fig. 1. The molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level.
	Fig. 2. Packing diagram of the title compound.

cis-4-(Tosyloxymethyl)cyclohexanecarboxylic acid top

Crystal data top

C₁₅H₂₀O₅S	F(000) = 664
M_r = 312.37	D_x = 1.309 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 12.545 (4) Å	Cell parameters from 43 reflections
b = 10.085 (3) Å	θ = 4.4–7.3°
c = 12.654 (6) Å	µ = 0.22 mm⁻¹
β = 98.05 (3)°	T = 291 K
V = 1585.1 (10) Å³	Block, colourless
Z = 4	0.45 × 0.40 × 0.38 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.004
Radiation source: fine-focus sealed tube	θ_max = 25.5°, θ_min = 1.6°
Graphite monochromator	h = −15→15
ω/2θ scans	k = 0→12
4142 measured reflections	l = −6→15
2931 independent reflections	3 standard reflections every 250 reflections
1794 reflections with I > 2σ(I)	intensity decay: 0.8%

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.044	H-atom parameters constrained
wR(F²) = 0.130	w = 1/[σ²(F_o²) + (0.0689P)² + 0.1341P] where P = (F_o² + 2F_c²)/3
S = 1.03	(Δ/σ)_max < 0.001
2931 reflections	Δρ_max = 0.24 e Å⁻³
197 parameters	Δρ_min = −0.26 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0109 (15)

Crystal data top

C₁₅H₂₀O₅S	V = 1585.1 (10) Å³
M_r = 312.37	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 12.545 (4) Å	µ = 0.22 mm⁻¹
b = 10.085 (3) Å	T = 291 K
c = 12.654 (6) Å	0.45 × 0.40 × 0.38 mm
β = 98.05 (3)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.004
4142 measured reflections	3 standard reflections every 250 reflections
2931 independent reflections	intensity decay: 0.8%
1794 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.044	0 restraints
wR(F²) = 0.130	H-atom parameters constrained
S = 1.03	Δρ_max = 0.24 e Å⁻³
2931 reflections	Δρ_min = −0.26 e Å⁻³
197 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	0.88825 (5)	1.11227 (6)	0.13440 (6)	0.0571 (2)
O1	0.86629 (16)	1.13334 (18)	0.24047 (15)	0.0714 (6)
O2	0.92693 (13)	0.96607 (16)	0.12094 (14)	0.0587 (5)
O3	0.96662 (14)	1.19132 (18)	0.09296 (16)	0.0734 (6)
O4	0.61080 (15)	0.4878 (2)	0.08885 (17)	0.0756 (6)
O5	0.60020 (17)	0.5097 (3)	−0.08567 (17)	0.0921 (7)
H5	0.5356	0.5095	−0.0812	0.138*
C1	0.6708 (2)	1.1419 (3)	0.0859 (2)	0.0655 (7)
H1	0.6689	1.1457	0.1591	0.079*
C2	0.5771 (2)	1.1563 (3)	0.0140 (3)	0.0768 (9)
H2	0.5122	1.1706	0.0399	0.092*
C3	0.5778 (2)	1.1499 (3)	−0.0942 (3)	0.0718 (8)
C4	0.6745 (3)	1.1276 (3)	−0.1305 (2)	0.0744 (8)
H4	0.6763	1.1214	−0.2035	0.089*
C5	0.7684 (2)	1.1143 (3)	−0.0613 (2)	0.0673 (7)
H5A	0.8331	1.1002	−0.0876	0.081*
C6	0.7667 (2)	1.1218 (2)	0.0466 (2)	0.0517 (6)
C7	0.4746 (3)	1.1693 (4)	−0.1705 (3)	0.1080 (12)
H7A	0.4173	1.1920	−0.1309	0.162*
H7B	0.4569	1.0887	−0.2094	0.162*
H7C	0.4843	1.2394	−0.2196	0.162*
C8	0.8744 (2)	0.8621 (2)	0.1757 (2)	0.0574 (7)
H8A	0.8005	0.8870	0.1802	0.069*
H8B	0.9116	0.8509	0.2477	0.069*
C9	0.87667 (18)	0.7337 (2)	0.11476 (18)	0.0475 (6)
H9	0.9516	0.7140	0.1065	0.057*
C10	0.8351 (2)	0.6228 (2)	0.1803 (2)	0.0537 (6)
H10A	0.8800	0.6170	0.2490	0.064*
H10B	0.7623	0.6434	0.1926	0.064*
C11	0.8356 (2)	0.4903 (2)	0.1233 (2)	0.0628 (7)
H11A	0.9095	0.4643	0.1201	0.075*
H11B	0.8036	0.4237	0.1644	0.075*
C12	0.7748 (2)	0.4936 (3)	0.0110 (2)	0.0618 (7)
H12	0.7914	0.4111	−0.0242	0.074*
C13	0.8138 (2)	0.6083 (3)	−0.0531 (2)	0.0620 (7)
H13A	0.8869	0.5905	−0.0659	0.074*
H13B	0.7687	0.6138	−0.1218	0.074*
C14	0.81088 (19)	0.7401 (2)	0.00422 (18)	0.0509 (6)
H14A	0.7369	0.7627	0.0108	0.061*
H14B	0.8396	0.8090	−0.0373	0.061*
C15	0.6550 (2)	0.4981 (2)	0.0095 (2)	0.0608 (7)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0529 (4)	0.0520 (4)	0.0648 (5)	−0.0071 (3)	0.0025 (3)	−0.0085 (3)
O1	0.0762 (13)	0.0768 (13)	0.0589 (12)	−0.0026 (10)	0.0017 (10)	−0.0190 (9)
O2	0.0526 (10)	0.0551 (10)	0.0697 (12)	−0.0066 (8)	0.0133 (9)	−0.0022 (8)
O3	0.0561 (12)	0.0641 (11)	0.0990 (15)	−0.0186 (9)	0.0074 (10)	0.0001 (10)
O4	0.0562 (12)	0.1058 (16)	0.0645 (13)	−0.0209 (10)	0.0070 (10)	−0.0001 (11)
O5	0.0640 (13)	0.139 (2)	0.0713 (14)	−0.0219 (14)	0.0036 (11)	0.0193 (13)
C1	0.0573 (17)	0.0739 (18)	0.0659 (18)	−0.0063 (14)	0.0111 (15)	−0.0126 (14)
C2	0.0484 (17)	0.091 (2)	0.091 (2)	−0.0003 (15)	0.0110 (16)	−0.0210 (18)
C3	0.0640 (19)	0.0699 (18)	0.077 (2)	−0.0004 (14)	−0.0058 (17)	−0.0145 (15)
C4	0.076 (2)	0.089 (2)	0.0558 (18)	0.0038 (17)	0.0018 (16)	−0.0006 (15)
C5	0.0593 (17)	0.0799 (19)	0.0640 (19)	0.0029 (14)	0.0128 (15)	−0.0006 (14)
C6	0.0525 (15)	0.0462 (13)	0.0558 (15)	−0.0047 (11)	0.0055 (12)	−0.0056 (11)
C7	0.077 (2)	0.130 (3)	0.106 (3)	0.012 (2)	−0.025 (2)	−0.018 (2)
C8	0.0589 (16)	0.0625 (16)	0.0506 (15)	−0.0092 (12)	0.0071 (13)	0.0009 (12)
C9	0.0410 (13)	0.0525 (13)	0.0482 (14)	−0.0033 (11)	0.0035 (11)	0.0020 (11)
C10	0.0464 (14)	0.0613 (15)	0.0517 (14)	−0.0021 (12)	0.0010 (11)	0.0106 (12)
C11	0.0499 (15)	0.0558 (15)	0.082 (2)	0.0018 (12)	0.0072 (14)	0.0111 (13)
C12	0.0616 (17)	0.0529 (14)	0.0721 (19)	−0.0055 (12)	0.0138 (14)	−0.0088 (12)
C13	0.0559 (15)	0.0810 (18)	0.0511 (15)	−0.0119 (14)	0.0144 (13)	−0.0095 (14)
C14	0.0487 (14)	0.0576 (14)	0.0466 (14)	−0.0070 (11)	0.0070 (11)	0.0062 (11)
C15	0.0596 (17)	0.0564 (15)	0.0647 (19)	−0.0165 (13)	0.0023 (15)	0.0002 (13)

Geometric parameters (Å, º) top

S1—O3	1.4218 (18)	C7—H7C	0.9600
S1—O1	1.423 (2)	C8—C9	1.510 (3)
S1—O2	1.5688 (18)	C8—H8A	0.9700
S1—C6	1.759 (3)	C8—H8B	0.9700
O2—C8	1.464 (3)	C9—C14	1.523 (3)
O4—C15	1.217 (3)	C9—C10	1.526 (3)
O5—C15	1.306 (3)	C9—H9	0.9800
O5—H5	0.8200	C10—C11	1.519 (3)
C1—C6	1.380 (4)	C10—H10A	0.9700
C1—C2	1.390 (4)	C10—H10B	0.9700
C1—H1	0.9300	C11—C12	1.516 (4)
C2—C3	1.372 (4)	C11—H11A	0.9700
C2—H2	0.9300	C11—H11B	0.9700
C3—C4	1.374 (4)	C12—C15	1.501 (4)
C3—C7	1.515 (4)	C12—C13	1.532 (4)
C4—C5	1.372 (4)	C12—H12	0.9800
C4—H4	0.9300	C13—C14	1.517 (3)
C5—C6	1.371 (4)	C13—H13A	0.9700
C5—H5A	0.9300	C13—H13B	0.9700
C7—H7A	0.9600	C14—H14A	0.9700
C7—H7B	0.9600	C14—H14B	0.9700

O3—S1—O1	119.95 (12)	C8—C9—C10	108.55 (19)
O3—S1—O2	104.28 (11)	C14—C9—C10	110.34 (18)
O1—S1—O2	110.26 (11)	C8—C9—H9	108.4
O3—S1—C6	108.65 (12)	C14—C9—H9	108.4
O1—S1—C6	108.78 (13)	C10—C9—H9	108.4
O2—S1—C6	103.69 (10)	C11—C10—C9	111.2 (2)
C8—O2—S1	117.09 (15)	C11—C10—H10A	109.4
C15—O5—H5	109.5	C9—C10—H10A	109.4
C6—C1—C2	118.7 (3)	C11—C10—H10B	109.4
C6—C1—H1	120.7	C9—C10—H10B	109.4
C2—C1—H1	120.7	H10A—C10—H10B	108.0
C3—C2—C1	121.7 (3)	C12—C11—C10	113.0 (2)
C3—C2—H2	119.2	C12—C11—H11A	109.0
C1—C2—H2	119.2	C10—C11—H11A	109.0
C2—C3—C4	118.1 (3)	C12—C11—H11B	109.0
C2—C3—C7	120.3 (3)	C10—C11—H11B	109.0
C4—C3—C7	121.6 (3)	H11A—C11—H11B	107.8
C5—C4—C3	121.5 (3)	C15—C12—C11	112.6 (2)
C5—C4—H4	119.3	C15—C12—C13	111.4 (2)
C3—C4—H4	119.3	C11—C12—C13	110.9 (2)
C6—C5—C4	119.9 (3)	C15—C12—H12	107.2
C6—C5—H5A	120.1	C11—C12—H12	107.2
C4—C5—H5A	120.1	C13—C12—H12	107.2
C5—C6—C1	120.2 (3)	C14—C13—C12	112.2 (2)
C5—C6—S1	119.5 (2)	C14—C13—H13A	109.2
C1—C6—S1	120.2 (2)	C12—C13—H13A	109.2
C3—C7—H7A	109.5	C14—C13—H13B	109.2
C3—C7—H7B	109.5	C12—C13—H13B	109.2
H7A—C7—H7B	109.5	H13A—C13—H13B	107.9
C3—C7—H7C	109.5	C13—C14—C9	110.81 (19)
H7A—C7—H7C	109.5	C13—C14—H14A	109.5
H7B—C7—H7C	109.5	C9—C14—H14A	109.5
O2—C8—C9	109.29 (19)	C13—C14—H14B	109.5
O2—C8—H8A	109.8	C9—C14—H14B	109.5
C9—C8—H8A	109.8	H14A—C14—H14B	108.1
O2—C8—H8B	109.8	O4—C15—O5	121.8 (3)
C9—C8—H8B	109.8	O4—C15—C12	123.9 (3)
H8A—C8—H8B	108.3	O5—C15—C12	114.3 (3)
C8—C9—C14	112.73 (19)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5···O4ⁱ	0.82	1.83	2.642 (3)	173

Symmetry code: (i) −x+1, −y+1, −z.

Experimental details

Crystal data
Chemical formula	C₁₅H₂₀O₅S
M_r	312.37
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	291
a, b, c (Å)	12.545 (4), 10.085 (3), 12.654 (6)
β (°)	98.05 (3)
V (Å³)	1585.1 (10)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.22
Crystal size (mm)	0.45 × 0.40 × 0.38

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	4142, 2931, 1794
R_int	0.004
(sin θ/λ)_max (Å⁻¹)	0.606

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.130, 1.03
No. of reflections	2931
No. of parameters	197
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.26

Computer programs: DIFRAC (Gabe et al., 1993), NRCVAX (Gabe et al., 1989), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5···O4ⁱ	0.82	1.83	2.642 (3)	173.0

Symmetry code: (i) −x+1, −y+1, −z.

References

Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Gabe, E. J., Le Page, Y., Charland, J.-P., Lee, F. L. & White, P. S. (1989). J. Appl. Cryst. 22, 384–387. CrossRef CAS Web of Science IUCr Journals Google Scholar
Gabe, E. J., White, P. S. & Enright, G. D. (1993). DIFRAC. American Crystallographic Association, Pittsburgh Meeting, Abstract PA 104. Google Scholar
Hoshina, K., Yamazaki, Y., Takeshita, T. & Naruchi, T. (1984). IUPHAP 9th International Congress of Pharmacology, p. 697. London. Google Scholar
Koningsveld, H. van (1972). Acta Cryst. B28, 1189–1195. CSD CrossRef IUCr Journals Web of Science Google Scholar
Qi, Q.-R., Huang, W.-C. & Zheng, H. (2008). Acta Cryst. E64, o405. Web of Science CSD CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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doi:10.1107/S1600536808003176

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