Crystal structure of S-1-[(carboxymethyl)sulfanyl]- N-(2-oxotetrahydro-3-thienyl)acetamide, C8H11NO4S2

Abstract

Source of materialErdosteine (S-1-[(carboxymethyl)sulfanyl]-N-(2-oxotetrahydro-3-thienyl)acetamide) wassynthesized according to the following route. Ethylc hloroacetate (ClCH 2 COOC 2 H 5 ,2 90 g, 2.4m o1) wasa dded into Na 2 S × 9H 2 O( 240 g, 1m ol) in ethyl acetate (200 mL). 3-Thioglutaric acid was recrystallized from and washed several times with ethyl acetate. Them ixture of 3-thioglutaric acid (75 g, 0.5 mol) and acetyl chloride (CH 3 COCl, 118 g, 1.3 mol) was refluxed for 3h.The extra acetyl chloride was removed under vacuum and the resultant residue was cooled to obtain asolid intermediate. 12 mol/L NaOH (5 mL) was added dropwise into thiolactone hydrochloride (31 g, 0.2 mol) in THF (100 mL), then the intermediate (29 g, 0.23 mol) in THF (100 mL) was added. The pH was adjusted to 7-8. Finally, 28 %aqueous ammonia (85 mL) was added to enantiomerically pure S-Erdosteine (300 g) in acetone (5 L).The collected precipitate in water (1 L) wasacidified to pH~3 with theaddition of 37 %HCl.The obtained S-Erdosteinew as filtereda nd driedu nder vacuum to give 250gofpurefinal product. Experimental detailsTheC -bound Ha toms were positioned geometricallya nd were reducedi nt he refinement in the riding model approximation, with d(C-H) =0.97 Åand U iso (H) =1.5U iso (C) for methylene CH. DiscussionThe title Erdosteine (S-1-[(carboxymethyl)sulfanyl]-N-(2-oxotetrahydro-3-thienyl)acetamide) was first disclosed in FRP 2, 502,153 and USP 4,411,909 [1,2]. It was introduced as a mucolytic agent for chronicp ulmonary diseases more than 15 years ago. The molecule contains two blocked sulfhydryl groups one of which, after hepatic metabolization and opening of thethiolactone ring,becomes available for pharmacological activity [3,4]. Thefree sulfhydrylgroup breaks the disulfide bridges of the high-molecular-weight mucus glycoproteins, resulting in reduced sputumphysical properties [5,6]. As tructural study of the title compound reveals the C-S and C-C bond distances in the tetrahydrothiophene ring to be 1.750 (4)