Crystal structure of a dimeric 1-benzothiepin

1.1 Results and discussion

2H-1-Benzothietes are versatile synthons for the preparation of various S-heterocycles [7–13]. Diester 4, our starting compound, was prepared by the reaction of diethyl (Z)-4-diazo-2-ethoxy-pent-2-enedioate, and 2H-1-benzothiete in the presence of rhodium (II) acetate as catalyst [14]. We tried to transform 4 to the corresponding thiepin by ether cleavage with BBr₃ and dehydrobromination with NaOCH₃ (Scheme 1). Instead of the expected 1-benzothiepin diester, we got a multicomponent mixture, which refrained from separation. However, after allowing an ethanol solution of the mixture to stand for several days at 0°C, we observed the formation of colorless crystals (13% yield). Their crystal structure analysis revealed the structure of the dimer meso-5. As its stereoselective formation is unlikely, we assume that the stereoisomers (R,R)-5 and (S,S)-5 were formed as well.

Scheme 1:

Formation of dimeric 1-benzothiepin derivatives.

Assuming that the dimerization proceeds via radical or ionic intermediates (Fig. 1), it may be expected that (R,R)-, (S,S)-, and (R,S)-2,2′-dimers as well as (2R,4′S)-, (2R,4′R)-, (2S,4′R)-, and (2S,4′S)-dimers could be formed in addition to (R,R)-5, (S,S)-5, and (R,S)-5. This might explain the complexity of the ¹H NMR spectra of the crude product.

Fig. 1:

Possible dimerization reactions of radical or ionic intermediates.

Figure 2 shows the Schakal plot, and Fig. 3 shows the unit cell of the X-ray diffraction of meso-5. The most important bond lengths, bond angles, and torsion angles are listed in Table 1.

Fig. 2:

Molecular structure of meso-5 in the crystalline state (Schakal plot).

Fig. 3:

Projection of the crystal structure of meso-5.

The length of the σ bond between the monomer units is extended to about 1.60 Å. The seven-membered rings are tilted against each other. Moreover, they are puckered, which is indicated by the torsion angles listed in Table 1.

3.1 Reaction of 4-ethoxy-4,5-dihydro- 1-benzothiepin-2,4-dicarboxylic acid diethyl ester (4)

To 4 (60 mg, 0.17 mmol), dissolved in 5 mL of dry CH₂Cl₂, a solution of 43 mg (0.17 mmol) BBr₃ in 2 mL of dry CH₂Cl₂ was added slowly at –78°C. The mixture was stirred overnight, and the reaction temperature was slowly raised to room temperature. Water (10 mL) was added, and the aqueous layer was extracted with 30 mL of CH₂Cl₂. The unified organic layers were evaporated at 0.1 kPa, and the residue was treated at ambient temperature with a solution of Na (23 mg, 1.0 mmol) in 10 mL of anhydrous ethanol. A ¹H NMR probe in CDCl₃ revealed a complex mixture of products. However, after a few days at 0°C, colorless crystals of meso-5 (6.8 mg, 13%, m.p. 137°C) could be collected from the ethanol phase.

3.2 Crystal structure analysis

Details of the crystal structure analysis of meso-5 are summarized in Table 2. The measurement was performed with an Enraf-Nonius CAD-4 diffractometer applying the Enraf Nonius Software V5 [16]. Structure solution and refinement were done with the programs Sir-97 [17] and Shelxl-97 [18].

CCDC 150223 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre viawww.ccdc.cam.ac.uk/data_request/cif.