4-[(4-Meth­oxy­benzene­sulfonamido)­meth­yl]cyclo­hexane-1-carb­oxy­lic acid

Muhammad Ashfaq; Samina Iram; Mehmet Akkurt; Islam Ullah Khan; Ghulam Mustafa; Muhammad Danish

doi:10.1107/S1600536811030650

. 2011 Aug 6;67(Pt 9):o2248–o2249. doi: 10.1107/S1600536811030650

4-[(4-Methoxybenzenesulfonamido)methyl]cyclohexane-1-carboxylic acid

Muhammad Ashfaq ^a, Samina Iram ^a, Mehmet Akkurt ^b,^*, Islam Ullah Khan ^c,^‡, Ghulam Mustafa ^a, Muhammad Danish ^a

PMCID: PMC3200917 PMID: 22058911

Abstract

In the title compound, C₁₅H₂₁NO₅S, two crystallographically independent molecules are linked into a dimer by a pair of N—H⋯O hydrogen bonds, forming an R ₂ ²(8) ring motif. In the crystal, molecules are further linked by intermolecular O—H⋯O hydrogen bonds into a two-dimensional network parallel to (012). Additional stabilization is provided by weak intermolecular C—H⋯O hydrogen bonds.

Related literature

For background to tranexamic acid (trans-4-(aminomethyl)cyclohexanecarboxylic acid), see: Boylan et al. (1996 ▶); Khan et al. (2002 ▶); Nilsson (1980 ▶); Shah et al. (2010 ▶); Shahzadi et al. (2007 ▶); Svahn et al. (1986 ▶); Vavrova et al. (2005 ▶). For a related structure, see: Ashfaq et al. (2011 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For ring conformations, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₅H₂₁NO₅S
M _r = 327.40
Triclinic,
a = 5.9119 (3) Å
b = 10.7223 (7) Å
c = 26.6453 (15) Å
α = 79.736 (3)°
β = 89.813 (3)°
γ = 75.518 (3)°
V = 1607.67 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 296 K
0.25 × 0.19 × 0.14 mm

Data collection

Bruker APEXII CCD diffractometer
25440 measured reflections
5942 independent reflections
3973 reflections with I > 2σ(I)
R _int = 0.048

Refinement

R[F ² > 2σ(F ²)] = 0.070
wR(F ²) = 0.218
S = 1.03
5942 reflections
412 parameters
5 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.92 e Å⁻³
Δρ_min = −0.36 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; 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: WinGX (Farrugia, 1999 ▶) and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811030650/lh5293sup1.cif

e-67-o2248-sup1.cif^{(34.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811030650/lh5293Isup2.hkl

e-67-o2248-Isup2.hkl^{(290.9KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811030650/lh5293Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O8ⁱ	0.83 (4)	2.14 (3)	2.961 (4)	173 (3)
N2—H2N⋯O3ⁱⁱ	0.85 (3)	2.18 (3)	3.024 (4)	172 (3)
O4—H4O⋯O5ⁱⁱⁱ	0.83 (5)	1.84 (5)	2.660 (5)	166 (6)
O10—H10O⋯O9^iv	0.82 (7)	1.89 (8)	2.631 (8)	151 (7)
C16—H16B⋯O6^v	0.96	2.59	3.378 (7)	139
C25—H25A⋯O3ⁱⁱ	0.97	2.54	3.450 (6)	157

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

The authors are grateful to the Vice Chancellor of the University of Gujrat, Professor Dr Nizamuddin, for creating a healthy research environment in the campus.

supplementary crystallographic information

Comment

Tranexamic acid or trans-4-(aminomethyl)cyclohexanecarboxylic acid, is a synthetic amino acid used commonly for curing abnormal bleeding in a variety of diseases (Boylan et al., 1996; Nilsson, 1980). A number of scientists derivatized this drug, evaluated the activity and found most derivatives were superior to the parent drug (Svahn et al., 1986; Khan et al., 2002; Vavrova et al., 2005; Shahzadi et al., 2007; Shah et al., 2010). We have recently prepared a derivative of this drug and reported the crystal structure (Ashfaq et al., 2011).

Fig. 1 shows the two crystallographically independent molecules in the asymmetric unit of the title compound (I). The molecules form a dimer, in which a pair of N—H···O hydrogen bonds generate an intermolecular R₂²(8) ring (Bernstein, et al., 1995). The cyclohexane rings (C9–C14 and C24–C29) in each molecule adopt a chair configuration [the puckering parameters are Q_T = 0.547 (5) Å, θ = 180.0 (5) °, φ = 286 (35) ° and Q_T = 0.561 (6) Å, θ = 3.7 (5) °, φ = 161 (8) °, respectively] (Cremer & Pople, 1975). In the crystal, molecules are further linked by intermolecular O—H···O hydrogen bonds to form a two-dimensional network parallel to (012). Additional stabilization is provided by weak intermoleclar C—H···O hydrogen bonds (Fig. 2).

Experimental

4-Methoxybenzene sulfonyl chloride (1.32 g, 6.36 mmol) was added to a solution of tranexamic acid (1.0 g, 6.36 mmol) in distilled water (10 ml). The reaction mixture was stirred at room temperature at pH 8–9, which was adjusted by 1M sodium carbonate solution. After completion of the reaction which was observed by the consumption of 4-methoxybenzene sulfonyl chloride, the pH was adjusted at 2–3 using 1 N HCl solution, which resulted in the formation of precipiates. these were filtered off and dried. The product was recrystallized using methanol.