(2S)-Methyl 2-(p-toluenesulfonamido)propanoate

Tayyaba Syed; Shahid Hameed; Peter G Jones; Andrea Schmidt-Meier

doi:10.1107/S1600536809017371

. 2009 May 14;65(Pt 6):o1300. doi: 10.1107/S1600536809017371

(2S)-Methyl 2-(p-toluenesulfonamido)propanoate

Tayyaba Syed ^a, Shahid Hameed ^a,^*, Peter G Jones ^b, Andrea Schmidt-Meier ^b

PMCID: PMC2969690 PMID: 21583158

Abstract

The enantiomerically pure title compound, C₁₁H₁₅NO₄S, contains a pyramidal N atom with an S—N bond length of 1.6262 (8) Å. In the crystal, molecules are linked to form chains parallel to the a axis by the hydrogen bond from NH to the carbonyl oxygen. C—H⋯O interactions are also present.

Related literature

For the applications of esters in the food and cosmetics industries, see: Soni et al. (2002 ▶). For their use as intermediates in the synthesis of heterocyclic compounds, see: Akhtar et al. (2007 ▶); Chen et al. (2007 ▶); Kucukguzel et al. (2007 ▶). For their use in the pharmaceutical industry, see: Iqbal & Chaudhry (2008 ▶). For the pharmacological activity of sulfonamides, see:Akhtar et al. (2008 ▶); Zareef et al. (2007 ▶). For a description of the Cambridge Structural Database, see: Allen (2002 ▶).

Experimental

Crystal data

C₁₁H₁₅NO₄S
M _r = 257.30
Orthorhombic,
a = 7.1948 (2) Å
b = 11.2552 (3) Å
c = 15.3311 (4) Å
V = 1241.50 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.26 mm⁻¹
T = 100 K
0.35 × 0.30 × 0.20 mm

Data collection

Oxford Diffraction Xcalibur E diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008 ▶) T _min = 0.972, T _max = 1.000 (expected range = 0.922–0.949)
55416 measured reflections
4284 independent reflections
4060 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.022
wR(F ²) = 0.063
S = 1.05
4284 reflections
161 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.31 e Å⁻³
Absolute structure: Flack (1983 ▶), 1818 Friedel pairs
Flack parameter: 0.01 (4)

Data collection: CrysAlis CCD (Oxford Diffraction, 2008 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2008 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP (Siemens, 1994 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809017371/hg2507sup1.cif

e-65-o1300-sup1.cif^{(17.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809017371/hg2507Isup2.hkl

e-65-o1300-Isup2.hkl^{(210KB, hkl)}

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
N—H01⋯O1ⁱ	0.865 (16)	2.057 (16)	2.9097 (10)	168.6 (14)
C10—H10⋯O1ⁱ	0.95	2.62	3.3696 (11)	136
C9—H9⋯O2ⁱⁱ	0.95	2.63	3.4065 (11)	140
C7—H7⋯O3ⁱⁱⁱ	0.95	2.67	3.6167 (11)	172
C4—H4C⋯O4^iv	0.98	2.49	3.3453 (13)	145

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

Acknowledgments

The authors are grateful to the Higher Education Commission of Pakistan for financial support through project Nos. 20–674/R & D/06/1764 under the National Research Program for Universities.

supplementary crystallographic information

Comment

Because of their versatility and harmlessness, esters have found many applications in the food and cosmetics industries (Soni et al., 2002). They have been reported as emulsifiers, dispersants, or thickeners. In addition to their use as intermediates in the synthesis of a large number of heterocyclic compounds (Chen et al., 2007; Kucukguzel et al., 2007; Akhtar et al., 2007), esters have also been used in the pharmaceutical industry as nervous system depressants, intestinal antiseptics and antibacterials (Iqbal et al., 2008). Sulfonamides, on the other hand, constitute an important class of drugs with several types of pharmacological activities (Akhtar et al., 2008; Zareef et al., 2007). The title compound (I) was synthesized in our laboratory as an intermediate for onward conversion to 1,3,4-oxadiazole derivatives, with a view to explore their anti-HIV and anti-HCV activities.

The molecule of (I) is shown in Fig. 1. Bond lengths and angles may be regarded as normal. In particular, the N—S bond length is 1.6262 (8) Å; a search of the Cambridge Database (Allen, 2002; Version 1.11) revealed 817 examples of the fragment Ph—SO₂—NH—C(sp³) (including substituted Ph rings) with a mean bond length of 1.614 Å. The nitrogen atom displays a pyramidal geometry, with N lying 0.293 (7) Å out of the plane of S, C2 and H01. The database hits showed a highly skewed distribution for this displacement, with many values of exactly zero; this is presumably attributable to fixing the hydrogen assuming planar geometry (AFIX 43 in the SHELX system), whereby the assumption of planarity is clearly not justified. Neglecting the zero values, the average deviation for 462 values is 0.24 Å. The sulfonyl group is oriented such that the bond S—O4 is approximately coplanar with the aromatic ring (torsion angle O4—S—C5—C6 - 6.70 (9)°).

The molecules are linked by classical hydrogen bonds from the NH group to the carbonyl oxygen (and not, as might have been expected, to a sulfonyl oxygen); the packing diagram (Fig. 2) shows chains of molecules parallel to the a axis. The four "weak" hydrogen bonds crosslink these chains to a three-dimensional pattern.

Experimental

Alanine (0.02 mol) was dissolved in an aqueous solution of potassium carbonate (0.06 mol, 50 ml) and a solution of 4-methylbenzenesulfonyl chloride (0.027 mol) in toluene (30 ml) was added. On completion of the reaction, the organic layer was separated and the aqueous layer acidified using dilute hydrochloric acid. The 2-(4-methylphenylsulfonylamino)propanoic acid thus obtained was filtered off and recrystallized from aqueous ethanol.

2-(4-Methylphenylsulfonylamino)propanoic acid (0.02 mol) was dissolved in methanol (30 ml), sulfuric acid (0.5 ml) was added and the mixture subjected to reflux while the reaction was monitored by TLC at regular intervals. After completion of the reaction, the reaction mixture was concentrated on the rotary evaporator to remove excess methanol. The product thus obtained was poured into water, neutralized with sodium bicarbonate and extracted with ethyl acetate (3 × 50 ml). The combined organic extracts were dried over anhydrous sodium sulfate and the solvent evaporated on a rotary evaporator. The product was recrystallized from acetone/water.