Crystal structure of methyl 1-(2-(fluorosulfonyl)ethyl)-2-oxocyclopentanecarboxylate, C₉H₁₃FO₅S

Source of material

A mixture of methyl 2-oxocyclopentane carboxylate (20 mg, 1.0 eq), thiourea (N,N-diisopropylethylamine; 0.20 eq) and DIPEA (0.20 eq) was stirred in toluene (1.0 mL) at room temperature. To this, ethenesulfonyl fluoride (3 eq) was added. The reaction progress was monitored by GC-MS. Upon completion, the reaction mixture was diluted with dichloromethane and passed through silica. The solvent was removed under reduced pressure to afford the product as a colourless oil (80%). Colourless oil, R_f = 0.44 (20% ethyl acetate/n-hexane). ¹H-NMR (CDCl₃, 400 MHz): 3.78 – 3.70 (1H, m), 3.68 (3H, s), 3.49 – 3.40 (1H, m), 2.50 – 2.42 (2H, m), 2.35 – 2.27 (1H, m), 2.24 – 2.19 (2H, m), 2.11 – 1.84(3H, m) ppm. ¹⁹F-NMR: 52.0 (1F, t, J_H-F = 5 Hz) ppm. ¹³C-NMR (CDCl₃, 100 MHz): 213.6, 171.0, 57.4, 53.0, 46.8 (d, J_C-F = 18 Hz), 38.0, 34.9, 27.2,19.6 ppm. The product was dissolved in n-hexane and subsequent evaporation yielded colourless crystals.

Experimental details

All hydrogen atoms were placed in idealised positions and refined in riding models with the U_iso values set to 1.2 or 1.5 times of those of their parent atoms and the constraint distances of C—H ranging from 0.95 Å to 1.00 Å.

Discussion

Sulfonyl fluorides (SF) are considered as a versatile functional group owing to its widespread applications [6], [7], [8], [9], [10]. The moiety has sparked interest in drug discovery, as it has shown to be an inhibitor for numerous proteins [11, 12] . Recently, the SF functional group has been included as a click reagent [13]. Despite this, there are very few references in the literature which highlight the SF group as synthetic intermediates. Currently, our work is aimed at fully investigating the synthetic potential of the SF group [14, 15] .

Crystal structure analysis of title compound revealed that the cyclopentane moiety of the molecule is distorted as the carbon atom C5 is tipped up towards the direction of methylcarboxylate moiety. The 2-(fluorosulfonyl)ethyl and methylcarboxylates substitutients attached are almost perpendicular to each other. The molecules in the crystals are interconnected through various C—H⋯O interactions. Among these, the two important C—H⋯O interactions that played a vital role in connecting the molecules in the crystals are formed between (i) the fluorosulfonyl group and cyclopentane H-atoms and (ii) fluorosulfonyl and methylcarboxlyate groups. Thus, these interactions help the molecules to form a layered structure made up by chains running along [110] plane. It is also important to note that the F-atom is not involved in any intermolecular interactions.