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Supporting Information Synthesis of Mono-Functionalized S-Diazocines

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Supporting Information Synthesis of Mono-Functionalized S-Diazocines Supporting Information for Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions Miriam Schehr1, Daniel Hugenbusch1, Tobias Moje1, Christian Näther2 and Rainer Herges*1 Address: 1Otto Diels-Institute for Organic Chemistry, Christian-Albrechts-University, Otto- Hahn-Platz 4, 24118 Kiel, Germany and 2Institute for Inorganic Chemistry, Christian- Albrechts-University, Max-Eyth-Str. 2, 24118 Kiel, Germany Email: Rainer Herges* - [email protected] * Corresponding author Analytical equipment, experimental procedures, spectral data and crystallographic data Table of contents I. Analytical equipment∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙S2–S3 II. Syntheses∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙S4–S27 III. Isolated byproduct reductive azo coupling∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙S28–S29 IV. UV–vis switching experiments∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙S30 V. Crystallographic data compound 3 ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙S31–S33 I. Analytical equipment NMR spectroscopy NMR spectra were measured in deuterated solvents (Deutero). To reference the NMR spectra the following solvent signals were used [1]: solvent degree of deuteration 1H signal 13C signal acetone-d6 99.8 % 2.05 (quintet) 29.84 (septet) chloroform-d1 99.8 % 7.26 (s) 77.16 (triplet) DMSO-d6 99.8 % 2.50 (s) 39.52 (septet) NMR measurements were performed with a Bruker DRX 500 (1H NMR: 500 MHz, 13C NMR: 125 MHz, 19F NMR: 470 MHz) and a Bruker AV 600 (1H NMR: 600 MHz, 13C NMR: 150 MHz) spectrometer. Signals were abbreviated with s, bs, d, t, m and mc for singlet, broad singlet, doublet, triplet, multiplet and centered multiplet. Melting point Melting points were measured with a Melting Point B-560 (Büchi) in melting point tubes. Mass spectrometry The high resolution (HR-EI) mass spectra were measured with an AccuTOF GCv 4G (Joel) with ionization energy of 70 eV and the high resolution (HR-ESI) mass spectra were measured with a Thermo Fischer Q Exactive Plus MS, Hybrid Quadrupol-Orbitrap. IR spectroscopy Infrared spectra were measured on a Perkin-Elmer 1600 Series FT-IR spectrometer with an A531-G Golden-Gate-Diamond-ATR-unit. Signals were abbreviated with w, m, s, vs for weak, medium, strong and very strong signal intensity. S2 UV–vis spectroscopy UV-Vis spectra were measured with a Lambda 650 spectrometer (Perkin-Elmer). Quartz cuvettes of 1 cm optical path length were used. Chromatography stationary phases For column chromatography purifications silica gel (Merck, particle size 0.040–0.063 mm) was used. Flash column chromatography purfications were performed on a Biotage® type Isolera one with Biotage® Ultra cartridges (Biotage®, HP-SphereTM, particle diameter: 25 μm, cartridges sizes: 10 g, 25 g, 50 g and 100 g) were used. Rf values were determined by thin layer chromatography on Polygram® SilG/UV254 (Macherey Nagel, 0.2 mm particle size). HPLC measurements Separation of the cis and trans isomers of compound 4 was performed using a HPLC (Agilent 1100 Series) with diode array UV/vis detector (Agilent 1200 Series). As stationary phase a reversed phase column type ZORBAX Eclipse XBD-C8 (Agilent, 150 × 46 mm, particle size: 5 µM) with an acetonitrile/water gradient as eluent was used. Light sources UV–vis and 1H NMR: The irradiation of the samples was performed with LEDs with a wavelength of 405 nm from SAHLMANN PHOTOCHEMICAL SOLUTIONS with followed specifications: 405 nm: 3 x NCSU276A-U405, FWHM = 13 nm, P (opt) = 3 x 1300 mW S3 II. Syntheses II.1. Synthesis of 4-bromo-1-(bromomethyl)-2-nitrobenzene (9) 4-Bromo-1-methyl-2-nitrobenzene (6) (2.00 g, 9.26 mmol), NBS (1.90 g, 10.7 mmol) and AIBN (160 mg, 0.97 mmol) were dissolved in 15 mL dry acetonitrile under nitrogen atmosphere. The mixture was refluxed under irradiation with light and after 24 h additional AIBN (160 mg, 0.97 mmol) was added. After 48 h the solvent was removed in vacuo and the crude product was purified by flash column chromatography (cyclohexane/chloroform, chloroform: 5% 29%) to yield a yellowish solid (1.69 g, 5.73 mmol, 62%). melting point: 73 °C. Rf : 0.44 (cyclohexane/chloroform, 4:1). 1 4 3 4 H NMR (500 MHz, CDCl3): δ = 8.19 (d, J = 2.01 Hz, 1 H, H-3), 7.74 (dd, J = 8.30 Hz, J = 2.01 Hz, 1 H, H-5), 7.46 (d, 3J = 8.30 Hz, 1 H, H-6), 4.77 (s, 2 H, H-7) ppm. 13 C NMR (125 MHz, CDCl3): δ = 148.2 (C-2), 136.7 (C-5), 133.8 (C-1), 131.8 (C-6), 128.5 (C-3), 122.9 (C-4), 27.9 (C-7) ppm. IR (ATR): ῦ = 3085 (w), 3053 (8) , 2864 (w), 1600 (w), 1562 (w), 1524 (vs), 1480 (m), 1435 (m), 1203 (w), 1225 (w), 1223 (w), 1126 (w), 1088 (m), 972 (w), 890 (m), 875 (m), 840 (m), 805 (s), 763 (m), 686 (s), 613 (s), 638 (w), 567 (m) cm-1. MS (EI, 70 eV): m/z (%) = 292 (6) [M]+, 213 (100) [M-Br]+. MS (EI, HR, 70 eV): C7H5Br2NO2, m/z = calc.: 292.8687, found: 292.8689. S4 Figure S1: 1H NMR spectrum of compound 9 measured in deuterated chloroform. Figure S2: 13C NMR spectrum of compound 9 measured in deuterated chloroform. S5 II.2. Synthesis of 4-iodo-1-(bromomethyl)-2-nitrobenzene (10) 4-Iodo-1-methyl-2-nitrobenzene (7) (3.60 g, 13.7 mmol), NBS (2.90 g, 16.3 mmol) and AIBN (70 mg, 0.43 mmol) were dissolved in 15 mL dry acetonitrile under nitrogen atmosphere. The mixture was refluxed under irradiation with light and after 24 h additional AIBN (150 mg, 0.91 mmol) was added. After 48 h the solvent was removed in vacuo. The crude product was filtered over silica gel with DCM and refluxed in 20 mL petroleum ether for 1 h. After filtration a beige solid was obtained. The yield was determined via 1H NMR which contains mostly a mixture of starting material 7 and desired product 10 (2.11 g, 6.17 mmol, 45%). 1 4 3 4 H NMR (500 MHz, CDCl3): δ = 8.35 (d, J = 1.77 Hz, 1 H, H-3), 7.93 (dd, J = 8.15 Hz, J = 1.7 Hz, 1 H, H-5), 7.30 (d, 3J = 8.15 Hz, H-6), 4.76 (s, 2 H, H-7) ppm. 13 C NMR (125 MHz, CDCl3): δ = 148.1 (C-4), 134.1 (C-3), 132.6 (C-1), 142.6 (C-5), 133.8 (C-6), 28.0 (C-7) ppm. MS (EI, 70 eV): m/z (%) = 341 (11) [M]+, 261 (100) [M-Br]+, 246 (78) [M-BrO]+. + MS (HR-ESI): m/z (%) = [C7H5BrINO2] , m/z = calc.: 340.8548, found.: 340.8545. S6 Figure S3: 1H NMR spectrum of compound 10 measured in deuterated chloroform. Figure S4: 13C NMR spectrum of compound 10 measured in deuterated chloroform. S7 II.3. General method for the synthesis of the substituted thioether derivatives 13-16: 2,2’-Disulfanediyldianiline (12) (0.55 equiv) was dissolved in dry THF under nitrogen atmosphere. Sodium borohydride (1.5 equiv) was added and the solution was heated at 60 °C for 1 h. In the process the initially yellow solution turns to a milky white. The solution was cooled to 45 °C and the substituted benzylchoride/bromide 8, 9, 10 or 11 (1 equiv) was added. After stirring for 1 h at 45 °C the solution was cooled to room temperature and diluted with water. The mixture was extracted with DCM, the combined organic layers were dried over magnesium sulfate, filtered and the solvent was removed in vacuo. The crude product was purified on silica using flash column chromatography. II.3.1. 2-((4-Chloro-2-nitrobenzyl)thio)aniline (13) 2,2’-Disulfanediyldianiline (12) (1.62 g, 6.51 mmol), sodium borohydride (671 mg, 17.7 mmol), 4- chloro-1-(chloromethyl)-2-nitrobenzene (8) (2.44 g, 11.8 mmol) in 40 mL dry THF. Flash chromatography: cyclohexane/ethyl acetate, ethyl acetate: 12% 100%. An orange solid was obtained (2.10 g, 7.12 mmol, 60%). melting point: 86 °C. Rf : 0.62 (cyclohexane/ethyl acetate, 1:1). 1 4 3 4 H NMR (500 MHz, CDCl3): δ = 7.96 (d, J = 2.2 Hz, 1 H, H-3), 7.34 (dd, J = 8.3 Hz, J = 2.2 Hz, 3 4 3 1 H, H-5), 7.13 (mc, 1 H, H-10), 7.04 (dd, J = 7.8 Hz, J = 1.5 Hz, 1 H, H-9), 6.91 (d, J = 8.3 Hz, 1 H, H-6), 6.70 (dd, 3J = 8.0 Hz, 4J = 1.3 Hz, 1 H, H-12), 6.57 (dt, 3J = 7.5 Hz, 4J = 1.3 Hz, 1 H, H- 11), 4.31 (bs, 1 H, 2 H, NH2), 4.21 (s, 2 H, H-7) ppm. 13 C NMR (125 MHz, CDCl3): δ = 148.9 (C-8), 148.5 (C-4), 137.1 (C-9), 133.7 (C-1), 133.3 (C-5), 132.7 (C-6), 132.5 (C-13), 130.9 (C-10), 125.3 (C-3), 118.5 (C-11), 115.4 (C-2), 114.9 (C-12), 35.6 (C-7) ppm. IR (ATR): ῦ = 3474 (m), 3376 (m), 1611 (m), 1566 (m), 1522 (s), 1478 (s), 1451 (m), 1432 (m), 1339 (vs), 1306 (m), 1255 (w), 1216 (w), 1160 (m), 1123 (m), 884 (m), 839 (m), 807 (m), 758 (vs), 735 (m), 714 (m), 656 (m), 530 (m) cm-1. + + MS (EI, 70 eV): m/z (%) = 294 (66) [M] , 124 (100) [M-C7H6ClNO2] . MS (EI, HR, 70 eV): [C13H11ClN2O2S], m/z = calc.: 294.0230, found: 294.0231. S8 Figure S5: 1H NMR spectrum of compound 13 measured in deuterated chloroform.
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