Crystal Structure of 2-(1-Benzoylazetidin-3-yl)thio-1,3-thiazoline

Abstract

Tebipenem pivoxil is an oral 1β-methylcarbapenem antibiotic with a broad spectrum and potent antibacterial activity against various bacteria, except for Pseudomonas aeruginosa, which has the [1-(1,3-thiazolin-2-yl)azetidin-3-yl]thio moiety as the pendant at the C-2 position.1 The pendant moiety of Tebipenem pivoxil was introduced using 1-(1,3-thiazolin-2-yl)azetidine-3thiol, and was also introduced into the antibiotic T405 under development.2 However, no chrystallographic studies of 1-(1,3-thiazolin-2-yl)azetidine-3-thiol and its synthetic precursors have been reported, except for Tebipenem pivoxil, which has the thio group.3 In this paper, we describe the X-ray crystal structure of 2-(1-benzoylazetidin-3-yl)thio-1,3-thiazoline (Fig. 1), which is a synthetic precursor of 1-(1,3-thiazolin-2-yl)azetidine-3-thiol. The title compound was synthesized by reacting 1-azabicyclo[1.1.0] butane and 3-benzoyl-1,3-thiazolidine-2-thione in the presence of a Lewis acid, such as Mg(OTf )2. Then, the crude compound was purified using column chromatography, followed by recrystallization from diethyl ether. Crystal data were collected on a Rigaku XtaLAB Synergy-i diffractometer (Rigaku Co., Tokyo, Japan) using the graphitemonochromated Cu-Kα radiation at 93.15 K, which are provided in Table 1. The initial structure was solved using an intrinsic phasing method with SHELXT-2018.5 All non-hydrogen atoms were refined using the full-matrix least-squares method on F2 by utilizing SHELXL-2018.6 All calculations were performed using Olex2 crystallographic software.7 Crystallographic data have been deposited to the Cambridge Crystallographic Data Center (CCDC-2075942). The absolute structure of this crystal was determined by X-ray diffraction method (Flack’s parameter: 0.006(11)). The ORTEP drawing is shown in Fig. 2, and selected bond lengths and angles are listed in Table 2. The S1– C4 bond length is 1.778(3)Å as a reasonable single-bond. The N2–C4 bond length of 1.256(4)Å is shorter than the N2–C6 bond length [1.472(4)Å] and is considered to form a double-bond. The thiazoline ring, defined by S1–C4–N2–C6–C5, forms a distorted five-membered ring from the ring strain (C4–S1–C5, 2021 © The Japan Society for Analytical Chemistry