2-Benzoyl-4-phenyl-1,2,5-thiadiazol-3(2H)-one 1,1-Dioxide

: 3,5-Diphenyl-4 H -1,2,6-thiadiazin-4-one treated with meta -chloroperoxybenzoic acid undergoes an oxidative ring contraction to give 2-benzoyl-4-phenyl-1,2,5-thiadiazol-3(2 H )-one 1,1-dioxide in a 29% yield, the structure of which is supported by single-crystal X-ray diffraction analysis and the available spectroscopic data.


Results and Discussion
Recently, we studied S-oxidations of 1,2,6-thiadiazines to access sulfoxide and sulfone analogs [15,16].In an attempt to explore the reactivity of thiadiazine 6a towards alternative oxidants, we expected to obtain thiadiazine sulfoxide 20 (Scheme 3).However, an unexpected discovery was made: when m-CPBA (four equiv. in total) was added to a DCM solution (C = 37.5 mM) of thiadiazine 6a, a gradual color change (from yellow to colorless) was observed over 24 h.This was not consistent with the structure of sulfoxide 20, as typically thiadiazine sulfoxides are colored [15,16].Upon working up the reaction mixture, colorless needles [mp 172-173 • C (from Et 2 O)] were isolated in a 29% yield.HRMS [m/z 315 (MH + )] revealed the addition of "O 2 ", suggesting oxidation had occurred, while the compound's lack of color [λ max (DCM) 295 nm, log ε 3.72] indicated a loss of the thiadiazine chromophore.The IR spectrum revealed two C=O stretching bands at 1772 and 1681 cm −1 and a strong band at 1300 cm −1 , suggesting the presence of a sulfone functionality. 1 H and 13 C NMR spectroscopy (see Supplementary Materials) supported an asymmetric structure and were similar to the spectra of 2-benzoyl-4-phenyl-1,2,5-thiadiazol-3(2H)-one 1-oxide (7a) [8].Furthermore, similar to thiadiazolone 7a, the product decomposed on silica.

Results and Discussion
Recently, we studied S-oxidations of 1,2,6-thiadiazines to access sulfoxide and sulfone analogs [15,16].In an attempt to explore the reactivity of thiadiazine 6a towards alternative oxidants, we expected to obtain thiadiazine sulfoxide 20 (Scheme 3).However, an unexpected discovery was made: when m-CPBA (four equiv. in total) was added to a DCM solution (C = 37.5 mM) of thiadiazine 6a, a gradual color change (from yellow to colorless) was observed over 24 h.This was not consistent with the structure of sulfoxide 20, as typically thiadiazine sulfoxides are colored Upon working up the reaction mixture, colorless needles [mp 172-173 °C (from Et2O)] were isolated in a 29% yield.HRMS [m/z 315 (MH + )] revealed the addition of "O2", suggesting oxidation had occurred, while the compound's lack of color [λmax(DCM) 295 nm, log ε 3.72] indicated a loss of the thiadiazine chromophore.The IR spectrum revealed two C=O stretching bands at 1772 and 1681 cm −1 and a strong band at 1300 cm −1 , suggesting the presence of a sulfone functionality. 1 H and 13 C NMR spectroscopy (see Supplementary Materials) supported an asymmetric structure and were similar to the spectra of 2-benzoyl-4-phenyl-1,2,5thiadiazol-3(2H)-one 1-oxide (7a) [8].Furthermore, similar to thiadiazolone 7a, the product decomposed on silica.X-Ray quality single crystals were prepared via the slow evaporation of an ethereal solution (5 mg in 1 mL) at ca. 20 °C, in the dark under air, and the structure was fully elucidated by single-crystal X-ray diffraction studies, revealing it to be the ring contracted sulfone, 2-benzoyl-4-phenyl-1,2,5-thiadiazol-3(2H)-one 1,1-dioxide (19) (Figure 2).X-Ray quality single crystals were prepared via the slow evaporation of an ethereal solution (5 mg in 1 mL) at ca. 20 • C, in the dark under air, and the structure was fully elucidated by single-crystal X-ray diffraction studies, revealing it to be the ring contracted sulfone, 2-benzoyl-4-phenyl-1,2,5-thiadiazol-3(2H)-one 1,1-dioxide (19) (Figure 2).The thiadiazole moiety is nearly planar with the plane defined by C1 N1 S1 N2 C2 with an RMSD of 0.033 Å.This plane is inclined at 15.954(8)° to the C bound Ph.However, the plane of the phenyl substituent of the benzoyl group is substantially out of the thiadiazole plane at 49.74(4)°.The carbonyl (C3 O4 N1 C4) is closer to coplanar with the The thiadiazole moiety is nearly planar with the plane defined by C1 N1 S1 N2 C2 with an RMSD of 0.033 Å.This plane is inclined at 15.954 (8) • to the C bound Ph.However, the plane of the phenyl substituent of the benzoyl group is substantially out of the thiadiazole plane at 49.74(4) • .The carbonyl (C3 O4 N1 C4) is closer to coplanar with the normal thiadiazole plane to normal plane angle, 16.485(9) • , and twisted with respect to the 4phenyl substituent at 37.12(3) • .The carbonyl oxygen of the thiadiazole moiety makes an intramolecular CH• • • O hydrogen bond with the phenyl H where C11• • • O3 is 2.943 Å.There are no significant intermolecular contacts.

Materials and Methods
All chemicals were commercially available except those whose synthesis is herein described.Anhydrous MgSO 4 was used for drying organic extracts and all volatiles were removed under reduced pressure.All reaction mixtures and column eluents were monitored by TLC using commercial glass-backed thin layer chromatography (TLC) plates (Merck Kieselgel 60 F 254 ).The plates were observed under UV light at 254 and 365 nm.The technique of flash chromatography was used throughout for all non-TLC scale chromatographic separations using Merck Silica Gel 60 (less than 0.063 mm).Melting points were determined using a Stuart SMP10 digital melting point apparatus.Small-scale (µL) liquid handling measurements were made using variable-volume (1.00-5000.00µL) single channel Gilson PIPETMAN precision micropipettes (Gilson, Middleton, WI, USA).The solvents used for recrystallisation are indicated after the melting point.IR spectra were recorded on a Thermo Scientific Nicolet iS5 FTIR spectrometer (Thermo Scientific, Waltham, MA, USA) with an iD5 ATR accessory and broad, strong, medium and weak peaks are represented by b, s, m and w, respectively. 1H and 13 NMR spectra were recorded on a Bruker AVANCE III HD machine [at 400 and 100 MHz, respectively (Bruker, Billerica, MA, USA)].An AVANCE III 300 MHz NMR Spectrometer was also used for reaction monitoring.Chemical shifts (δ) are expressed in ppm.Data are represented as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet and/or multiple resonances, br s = broad singlet).Deuterated solvents were used for homonuclear locks and the signals are referenced to the deuterated solvent peaks.For the acquisition of mass spectra, the samples were prepared as detailed below and analyzed by positive ion nanoelectrospray (nES) using a Thermo Scientific™ LTQ Orbitrap XL™ ETD Hybrid Ion Trap-Orbitrap Mass Spectrometer (Thermo Scientific, Waltham, MA, USA).For the X-ray crystallography, each crystal was coated in paraffin oil, mounted on a Molecular Dimensions Litholoop and placed directly into the cold stream of a Bruker D8 Venture diffractometer (Bruker, Billerica, MA, USA).Single-crystal X-ray diffraction data were collected using either a Cu-Kα (λ = 1.5418Å) IµS 3.0 microfocus source or a Mo sealed tube with Triumph monochromator, using Bruker's APEX3 program suite [17], with the crystal kept at 100.0 K during data collection.The structures were solved using Olex2 [18], using the SHELXT structure solution program [19], using Intrinsic Phasing, and refined with the SHELXL refinement package using Least Squares minimization [20].The starting materials 3,5-diphenyl-4H-1,2,6-thiadiazin-4-one 6a, dimethyl 4,4 ′ -(4-oxo-4H-1,2,6-thiadiazine-3,5diyl)dibenzoate (6b) and 3,5-bis(4-methoxyphenyl)-4H-1,2,6-thiadiazin-4-one (6c) were made according to the literature procedure [21].

Supplementary Materials:
The following information can be downloaded online: molfile, cif file, Figure S1:
1 H NMR spectrum of thiadiazole 19 in acetone-d 6 , FigureS2:13 C NMR spectrum of thiadiazole 19 in acetone-d 6 , Figure S3: IR spectrum, and Figure S4: Mass spectrum of thiadiazole 19.Author Contributions: E.B., A.S.K. and P.A.K. conceived the experiments; E.B. conducted the experiments; E.B. isolated and characterized compound 19; S.B.H.P. conducted experiments with additional substrates 6b and 6c; A.S.K. synthesized starting materials 6a-c; G.M.R. acquired and analyzed the SC-XRD data for compound 19; E.B. wrote the paper; E.B., A.S.K. and P.A.K. edited the manuscript.All authors have read and agreed to the published version of the manuscript.Funding: E.B. is grateful to the EPSRC CRITICAT Centre for Doctoral Training (E.B.Ph.D. Studentship: EP/L016419/1) for funding and training.S.B.H.P. acknowledges EaSI-CAT for funding.P.A.K. and A.S.K. thank the University of Cyprus for the Internal Grant "Thiadiazine-Based Organic Photovoltaics" and the Cyprus Research Promotion Foundation (Grant Nos.ΣTPATHII/0308/06, NEKYP/0308/02, ΥΓEIA/0506/19 and ENIΣX/0308/83).