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CC BY 4.0 · Synlett 2018; 29(02): 193-198
DOI: 10.1055/s-0036-1590920
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N1-Arylation of 1,4-Benzodiazepine-2-ones with Diaryliodonium Salts

Raysa Khan
a   Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, BN19QJ, UK   Email: j.spencer@sussex.ac.uk
,
Robert Felix
b   Tocris, Bio Techne, The Watkins Building, Atlantic Road, Bristol, BS11 9QD, UK
,
Paul D. Kemmitt
c   IMED Oncology, AstraZeneca, 310 Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK
,
Simon J. Coles
d   UK National Crystallography Service, Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK
,
Graham J. Tizzard
d   UK National Crystallography Service, Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK
,
John Spencer  *
a   Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, BN19QJ, UK   Email: j.spencer@sussex.ac.uk
› Author AffiliationsR.K. is funded by an EPSRC/AZ funded PhD studentship (EP/M507568/1) with additional support from AstraZeneca [14550001 (SME)] and Tocris Biosciences. The EPSRC is also thanked for funding the UK ­National Crystallography Service
Further Information

Publication History

Received: 13 July 2017

Accepted after revision: 06 September 2017

Publication Date:
25 September 2017 (online)

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Abstract

A library of N1-arylated 5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-ones has been synthesized starting with unsymmetrical diaryliodonium salts using aqueous ammonia as a base. This can also be applied to a similar 1,3,4-benzotriazepin-2-one derivative.

Key words

benzodiazepines - N-arylation - iodonium salt - privileged scaffold - benzotriazepine

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1590920.
  • Supporting Information
 

  • References and Notes

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  • 41 All reactions were conducted under an inert atmosphere unless specified otherwise. All commercially purchased materials and solvents were used without further purification unless specified otherwise. NMR spectra were recorded on a Varian VNMRS 500 (1H: 500 MHz, 13C: 126 MHz) spectrometer and prepared in deuterated solvents such as CDCl3 and DMSO-d 6. 1H and 13C chemical shifts were recorded in parts per million (ppm). Multiplicity of 1H NMR peaks are indicated by s – singlet, d – doublet, dd – doublets of doublets, t – triplet, pt – pseudo triplet, q – quartet, m – multiplet, and coupling constants are given in Hertz (Hz). Electrospray ionisation–high resolution mass spectra (ESI-HRMS) were obtained using a Bruker Daltonics Apex III where Apollo ESI was used as the ESI source. The molecular ion peaks [M]+ were recorded as mass to charge m/z ratio.
  • 42 LC–MS spectra were acquired using a Shimadzu LC-MS 2020, on a Gemini 5 µm C18 110 Å column and percentage purities were run over 30 min in water/acetonitrile with 0.1% formic acid (5 min at 5%, 5–95% over 20 min, 5 min at 95%) with the UV detector at 254 nm. Purifications were performed by flash chromatography on silica gel columns or C18 columns using a Combi flash RF 75 PSI, ISCO unit.General ProcedureTo a stirred solution of the appropriate 1,4-benzodiazepine or 1,3,4-benzotriazepine (0.030–1.00 mmol, 1 equiv) and diaryliodonium salt (0.033–1.10 mmol, 1.1 equiv) in DCE (5–10 mL) was added 25% w/w NH3 solution (aq. 5–10 mL), and the reaction mixture was stirred for 30 min (unless stated otherwise). Upon completion, the reaction mixture was diluted with dichloromethane (3 × 15 mL), and the layers were separated. Combined organic layers were dried (MgSO4), concentrated under reduced pressure, and purified by column chromatography, hexane/ethyl acetate (80:20 to 30:70).1-(4-Nitrophenyl)-5-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3a)The product was obtained as white solid (0.60 mmol scale, 170 mg, 96%). 1H NMR (500 MHz, CDCl3): δ = 8.27–8.21 (m, ArH, 2 H), 7.62 (dd, 3 J HH = 7.5, 1.5 Hz, ArH, 1 H), 7.40–7.35 (m, ArH, 3 H), 7.34–7.29 (m, ArH, 1 H), 6.82 (d, 3 JHH = 8.0 Hz, ArH, 1 H), 4.70 (d, 2 JHH = 10.5 Hz, COCH2, 1 H), 3.83 (d, 2 JHH = 10.5 Hz, COCH2, 1 H), 2.62 (s, CH3, 3 H). 13C NMR (126 MHz, CDCl3): δ = 170.1 (C=O), 168.1 (C=N), 146.7 (ArC), 146.0 (ArC), 140.8 (ArC), 131.4 (ArC), 131.3 (ArC), 128.7 (ArC × 2), 127.8 (ArC), 125.9 (ArC), 125.1 (ArC), 124.5 (ArC × 2), 56.6 (COCH2), 25.5 (CH3). ESI-HRMS: m/z calcd for C16H13N3O3 [+H]+: 296.1030; found: 296.1033. LC–MS purity (UV) = 100%, t R = 8.10 min.1-(4-Nitrophenyl)-5-(propan-2-yl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3b)The product was obtained as a white solid (0.52 mmol scale, 166 mg, 99%). 1H NMR (500 MHz, CDCl3): δ = 8.27–8.20 (m, ArH, 2 H), 7.59 (dd, 3 JHH = 7.5, 2.0 Hz, ArH, 1 H), 7.39–7.35 (m, ArH, 3 H), 7.34–7.30 (m, ArH, 1 H), 6.83 (dd, 3 JHH = 8.0, 1.5 Hz, ArH, 1 H), 4.72 (d, 2 JHH = 10.5 Hz, COCH2, 1 H), 3.82 (d, 2 JHH = 10.5 Hz, COCH2, 1 H), 3.34–3.25 (m, 1 H), 1.35 (d, 3 JHH = 7.0 Hz, CNCHC2CH 6, 3 H), 1.11 (d, 3 JHH = 7.0 Hz, CNCHC2CH 6, 3 H). 13C NMR (126 MHz, CDCl3): δ = 176.9 (C=O), 168.7 (C=N), 146.7 (ArC), 145.9 (ArC), 141.5 (ArC), 131.6 (ArC), 130.9 (ArC), 128.3 (ArC × 2), 127.0 (ArC), 126.0 (ArC), 125.0 (ArC), 124.5 (ArC × 2), 56.5 (COCH2), 35.6 (CNCHC2H6), 22.0 (CNCHC 2H6), 19.2 (CNCHC2H6). ESI-HRMS: m/z calcd for C18H17N3O3 [+H]+: 324.1270; found: 324.1281. LC–MS purity (UV) = 96 %, t R = 18.73 min.1-(4-Nitrophenyl)-3-(propan-2-yl)-5-(propan-2-yl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3c)The product was obtained as white solid (0.25 mmol scale, 91 mg, 99%). 1H NMR (500 MHz) CDCl3: δ = 8.25–8.18 (m, ArH, 2 H), 7.61 (dd, 3 JHH = 8.0, 1.5 Hz, ArH, 1H), 7.39–7.24 (m, ArH, 4 H), 6.85 (dd, J = 8.0, 1.5 Hz, ArH, 1 H), 3.27 (hept, 3 JHH = 7.0 Hz, CNCHCH3CH3, 1 H), 3.12 (d, 3 JHH = 9.5 Hz, COCHCHC2H6, 1 H), 2.72–2.61 (m, COCHCHC2H6, 1 H), 1.33 (d, 3 JHH = 7.0 Hz, CNCHC2 H 6, 3 H), 1.07 (d, 3 JHH = 7.0 Hz, CNCHC2CH 6, 3 H), 1.05–1.02 (m, COCHCHC2 H 6, 6 H). 13C NMR (126 MHz, CDCl3): δ = 173.9 (C=O), 168.3 (C=N), 147.4 (ArC), 145.7 (ArC), 141.1 (ArC), 131.9 (ArC), 130.6 (ArC), 128.4 (ArC × 2), 126.8 (ArC), 125.7 (ArC), 125.1 (ArC), 124.4 (ArC × 2), 69.3 (COCHCHC2H6), 35.5 (CNCHCH3CH3), 22.2 (COCHCHC2H6), 21.9 (CNCHC 2H6), 20.1, (CNCHC 2H6) 19.3 (COCHCHC 2H6), 18.7 (COCHCHC 2H6). ESI-HRMS: m/z calcd for C21H23N3O3 [+H]+: 366.1812; found: 366.1816. LC–MS purity (UV) = 95%, t R = 23.47 min.1-(4-Nitrophenyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3d)The product was obtained as white solid (0.60 mmol scale, 176 mg, 82%). 1H NMR (500 MHz, CDCl3): δ = 8.30–8.23 (m, ArH, 2 H), 7.77–7.71 (m, ArH, 2 H), 7.55–7.51 (m, ArH, 1 H), 7.49–7.45 (m, ArH, 3 H), 7.45–7.41 (m, ArH, 3 H), 7.29 (d, 3 JHH = 8.0 Hz, ArH, 1 H), 6.94 (d, 3 JHH = 8.0 Hz, ArH, 1 H), 4.96 (d, 2 JHH = 10.5 Hz, COCH 2, 1 H), 4.03 (d, 2 JHH = 10.5 Hz, COCH 2, 1 H). 13C NMR (126 MHz, CDCl3): δ = 170.3 (C=O), 168.3 (C=N), 146.7 (ArC), 146.0 (ArC), 142.7 (ArC), 138.4 (ArC), 131.4 (ArC), 130.8 (ArC), 130.4 (ArC), 130.3 (ArC), 129.4 (ArC × 2), 128.5 (ArC × 2), 128.4 (ArC × 2), 125.4 (ArC), 125.0 (ArC), 124.5 (ArC × 2), 57.4 (COCH2). ESI-HRMS: m/z calcd for C21H15N3O3 [+H]+: 358.1186; found: 358.1187. LC–MS purity (UV) = 95%, t R = 18.35 min.1-(4-Nitrophenyl)-3-benzyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3e)The product was obtained as white solid (0.40 mmol scale, 140 mg, 78%). 1H NMR (500 MHz, CDCl3): δ = 8.27–8.21 (m, ArH, 2 H), 7.67 (d, 3 JHH = 7.5 Hz, ArH, 2 H), 7.52–7.48 (m, 1 H), 7.47–7.43 (m, ArH, 2 H), 7.41–7.37 (m, ArH, 5 H), 7.36–7.30 (m, ArH, 3 H), 7.25–7.21 (m, ArH, 2 H), 6.90 (d, 3 JHH = 8.0 Hz, ArH, 1 H), 4.01 (dd, J = 7.5, 6.0 Hz, COCHCH2, 1 H), 3.68 (dd, 2,3 JHH = 14.0, 6.0 Hz, COCHCH 2, 1 H), 3.62 (dd, 2,3 JHH = 14.0, 7.5 Hz, COCHCH 2, 1 H). 13C NMR (126 MHz, CDCl3): δ = 168.8 (C=O), 168.5 (C=N), 147.1 (ArC), 145.9 (ArC), 142.1 (ArC), 138.9 (ArC), 138.4 (ArC), 131.5 (ArC), 130.8 (ArC), 130.5 (ArC), 130.3 (ArC), 130.0 (ArC × 2), 129.5 (ArC × 2), 128.6 (ArC × 2), 128.5 (ArC × 2), 128.3 (ArC × 2), 126.3 (ArC), 125.3 (ArC), 125.1 (ArC), 124.5 (ArC × 2), 65.6 (COCHCH2), 37.9 (COCHCH2). ESI-HRMS: m/z calcd for C28H21N3O3 [+H]+: 448.1656; found: 448.1669. LC–MS purity (UV) = 99 %, t R = 20.81 min.7-Chloro-1-(4-nitrophenyl)-3-benzyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3f)The product was obtained as white solid (0.15 mmol scale, 54 mg, 75%). 1H NMR (500 MHz, CDCl3): δ = 8.26 (d, 3 JHH = 8.5 Hz, ArH, 2 H), 7.66 (d, 3 JHH = 7.5 Hz, ArH, 2 H), 7.57–7.50 (m, ArH, 1 H), 7.51–7.44 (m, ArH, 2 H), 7.42–7.36 (m, ArH, 3 H), 7.34–7.30 (m, ArH, 2 H), 7.26 (s, ArH, 3 H), 7.17 (d, J = 8.7 Hz, ArH, 1 H), 6.85 (d, 3 JHH = 8.5 Hz, ArH, 1 H), 3.99 (dd, J = 7.5, 6.0 Hz, COCHCH2, 1 H), 3.70–3.57 (m, COCHCH 2, 2 H). 13C NMR (126 MHz, CDCl3): δ = 168.4, (C=O), 167.2 (C=N), 146.6 (ArC), 146.1 (ArC), 140.6 (ArC), 138.6 (ArC), 137.7 (ArC), 131.7 (ArC), 131.1 (ArC), 129.9 (ArC × 2), 129.8 (ArC), 129.5 (ArC × 2), 128.7 (ArC × 2), 128.6 (ArC × 2), 128.3 (ArC × 2), 126.5 (ArC), 126.4 (ArC), 126.2 (ArC), 124.6 (ArC × 2), 119.3 (ArC) 65.8 (COCHCH2), 37.9 (COCHCH2). ESI-HRMS: m/z calcd for C28H20ClN3O3 [+H]+: 482.1266; found: 482.1286. LC–MS purity (UV) = 95%, t R = 19.71 min. 1-(4-Nitrophenyl)-3-benzyl-5-(pyridine-2-yl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3g)The product was obtained as white solid (0.11 mmol scale, 38 mg, 77%). 1H NMR (500 MHz, CDCl3): δ = 8.67–8.62 (m, ArH, 1 H), 8.15 (d, 3 JHH = 8.0 Hz, ArH, 2 H), 8.18–8.12 (m, ArH, 1 H), 7.88–7.81 (m, ArH, 1 H), 7.44–7.42 (m, ArH, 2 H), 7.42–7.37 (m, ArH, 4 H), 7.35–7.26 (m, ArH, 3 H), 7.25–7.21 (m, ArH, 2 H), 6.89 (d, 3 JHH = 8.0 Hz, ArH, 1 H), 4.10 (dd, 3 JHH = 8.0, 6.0 Hz, COCHCH2, 1 H), 3.70 (dd, 2,3 JHH = 14.0, 7.0 Hz, COCHCH 2, 1 H), 3.62 (dd, 2,3 JHH = 14.0, 7.5 Hz, COCHCH 2, 1 H). 13C NMR (126 MHz, CDCl3): δ = 168.6 (C=O), 167.6 (C=N), 155.9 (ArC), 148.7 (ArC), 147.1 (ArC), 145.9 (ArC), 141.9 (ArC), 138.9 (ArC), 136.8 (ArC), 131.4 (ArC), 130.8 (ArC), 129.9 (ArC × 2), 128.8 (ArC × 2), 128.3 (ArC × 2), 126.3 (ArC), 125.2 (ArC), 125.1 (ArC), 124.8 (ArC × 2), 124.4 (ArC × 2), 123.8 (ArC), 65.8 (COCHCH2), 37.8 (COCHCH2). ESI-HRMS: m/z calcd for C27H20N4O3 [+H]+: 449.1608; found: 449.1617. LC–MS purity (UV) = 99%, t R = 20.81 min.1-(4-Nitrophenyl)-3-benzyl-5-(2′-fluorobiphenyl-2-yl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3h)The product was obtained as white solid (0.03 mmol scale, 11 mg, 70%). 1H NMR (500 MHz, CDCl3): δ = 8.14 (d, 3 JHH = 8.5 Hz, ArH, 2 H), 7.57–7.52 (m, ArH, 1 H), 7.51–7.45 (m, ArH, 1 H), 7.42 (d, 3 JHH = 7.5 Hz, ArH, 1 H), 7.38 (d, 3 JHH = 7.5 Hz, ArH, 1 H), 7.32–7.27 (m, ArH, 7 H), 7.26–7.19 (m, ArH, 2 H), 7.15–7.09 (m, ArH, 1 H), 7.06 (d, 3 JHH = 7.5 Hz, ArH, 1 H), 7.00–6.93 (m, ArH, 3 H), 6.65 (d, 3 JHH = 8.5 Hz, ArH, 1 H), 3.80 (dd, 3 JHH = 8.0, 5.5 Hz, COCHCH2, 1 H), 3.69 (d, 3 JHH = 8.0 Hz, COCHCH 2, 1 H), 3.66 (d, 3 JHH = 8.0 Hz, COCHCH 2, 1 H). 13C NMR (126 MHz, CDCl3): δ = 169.5 (C=O), 167.9 (C=N), 159.2 (d, 1 J FC = 247.5 Hz, ArC) 147.1 (ArC), 145.7 (ArC), 141.5 (ArC), 138.8 (ArC), 138.7 (ArC), 135.7 (ArC), 132.0 (d, 3 J FC = 3.5 Hz, ArC), 131.6 (ArC), 131.4 (ArC), 130.8 (ArC), 130.3 (ArC), 129.9 (ArC x 2), 129.8 (ArC), 129.5 (ArC), 129.2 (ArC), 128.9 (d, 3 J FC = 8.0 Hz, ArC), 128.5 (ArC × 2), 128.3 (ArC × 2), 128.1 (ArC), 126.3 (ArC), 125.2 (ArC), 124.8 (ArC), 124.5 (d, 4 J FC = 3.5 Hz, ArC), 124.2 (ArC x 2), 115.4 5 (d, 2 J FC = 22.0 Hz, ArC) 66.0 (COCHCH2), 37.8 (COCHCH2). ESI-HRMS: m/z calcd for C34H24N3O3 [+H]+: 542.1874; found: 542.1881. LC–MS purity (UV) = 93%, t R = 23.27 min.1-(2,4,6-Trimethylphenyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3i)The reaction was run for 8 h. The product was obtained as white solid (1.00 mmol scale, 181 mg, 51%). 1H NMR (500 MHz, DMSO-d 6): δ = 7.60–7.57 (m, ArH, 2 H), 7.54–7.46 (m, ArH, 4 H), 7.32 (d, 3 JHH = 8.0 Hz, ArH, 1 H), 7.27–7.23 (m, ArH, 1 H), 7.10–7.07 (m, ArH, 1 H), 6.88 (s, ArH, 1 H), 6.78 (d, 3 JHH = 8.0, 1.1 Hz, ArH, 1 H), 4.70 (d, 2 JHH = 10.0 Hz, COCH 2,1 H), 4.04 (d, 2 JHH = 10.0 Hz, COCH 2, 1 H), 2.26 (s, CH3, 3 H), 2.24 (s, CH3, 3 H), 1.61 (s, CH3, 3 H). 13C NMR (126 MHz, DMSO-d 6): δ = 170.3 (C=O), 167.5 (C=N), 142.2 (ArC), 138.9 (ArC), 137.9 (ArC), 137.0 (ArC), 136.2 (ArC), 134.7 (ArC), 132.3 (ArC), 130.9 (ArC), 130.0 (ArC × 2), 129.6 (ArC × 2), 129.5 (ArC), 128.9 (ArC × 2), 128.7 (ArC), 124.4 (ArC), 122.1 (ArC), 57.3 (COCH2), 21.0 (CH3), 18.5(CH3), 17.5 (CH3). ESI-HRMS: m/z calcd for C24H22N2O [+H]+: 355.1805; found: 355.1804. LC–MS purity (UV) = 97%, t R = 21.13 min.1-(2-Bromophenyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3j)The reaction was run for 8 h. The product was obtained as white solid (1.00 mmol scale, 31 mg, 8%). 1H NMR (500 MHz, DMSO-d 6): δ = 7.84 (d, 3 JHH = 8.0 Hz, ArH, 1 H), 7.70 (d, 3 JHH = 8.0 Hz, ArH, 1 H), 7.66–7.59 (m, ArH, 4 H), 7.52–7.46 (m, ArH, 3 H), 7.41–7.37 (m, ArH, 1 H), 7.32 (dd, J = 7.8, 1.7 Hz, ArH, 1 H), 7.27 (d, 3 JHH = 7.0 Hz, ArH, 1 H), 6.92–6.83 (m, ArH, 1 H), 4.69 (d, 2 JHH = 10.5 Hz, COCH 2, 1 H), 4.01 (d, 2 JHH = 10.5 Hz, COCH 2, 1 H). 13C NMR (126 MHz, CDCl3): δ = 170.7 (C=O), 168.9 (C=N), 142.0 (ArC), 138.9 (ArC), 138.6 (ArC), 134.3 (ArC), 133.7 (ArC), 132.0 (ArC), 131.0 (ArC), 130.9 (ArC), 130.8 (ArC), 129.9 (ArC × 2), 129.8 (ArC), 129.1 (ArC), 128.8 (ArC × 2), 124.7 (ArC), 123.0 (ArC), 121.5 (ArC), 57.0 (COCH2). ESI-HRMS: m/z calcd for C21H15BrN2O [+H]+: 391.0441; found: 391.0457. LC–MS purity (UV) = 93%, t R = 15.23 min.1-(3′-Trifluoromethylphenyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3k)The reaction was run for 8 h. The product was obtained as white solid (0.50 mmol scale, 80 mg, 42%). 1H NMR (500 MHz, CDCl3): δ = 7.72 (d, 3 JHH = 7.5 Hz, ArH, 2 H), 7.60–7.55 (m, ArH, 2 H), 7.53 (d, 3 JHH = 8.5 Hz, ArH, 2 H), 7.49–7.45 (m, ArH, 2 H), 7.44–7.38 (m, ArH, 3 H), 7.25–7.20 (m, ArH, 1 H), 6.92 (d,3 JHH = 8.5 Hz, ArH, 1 H), 4.95 (d, 2 JHH = 10.5 Hz, COCH 2, 1 H), 4.02 (d, 2 JHH = 10.5 Hz, COCH 2, 1 H). 13C NMR (126 MHz, CDCl3): δ = 170.3 (C=O), 168.3 (C=N), 143.1 (ArC), 141.3 (ArC), 138.6 (ArC), 132.0 (q, 2 J FC = 29.9 Hz, ArC), 131.9 (ArC), 131.6 (ArC), 131.4 (ArC), 130.7 (ArC), 130.4 (ArC), 129.8 (ArC × 2), 129.5 (ArC), 128.5 (ArC × 2), 125.2 (q, 3 J FC = 3.5 Hz, ArC), 124.8 (ArC), 124.8 (ArC), 123.5 (q, 1 J FC = 273.0 Hz, ArC), 124.2 (q, 3 J FC = 3.5 Hz, ArC), 57.3 (COCH2). ESI-HRMS: m/z calcd for C22H15F3N2O [+H]+: 381.1209; found: 381.1208. LC–MS purity (UV) = 96%, t R = 21.35 min.1-Phenyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (3l)The reaction was run for 8 h. The product was obtained as white solid (0.50 mmol scale, 14 mg, 9%). 1H NMR (500 MHz, CDCl3): δ = 7.72 (d, 3 JHH = 7.5 Hz, ArH, 2 H), 7.54–7.49 (m, ArH, 1 H), 7.47 (d, 3 JHH = 7.5 Hz, ArH, 2 H), 7.43–7.38 (m, ArH, 2 H), 7.37–7.30 (m, ArH, 2 H), 7.24–7.21 (m, ArH, 3 H), 7.20–7.16 (m, ArH, 1 H), 6.97 (d, 3 JHH = 8.5 Hz, ArH, 1 H), 4.96 (d, 2 JHH = 10.5 Hz, ArH, COCH 2, 1 H), 4.01 (d, 2 JHH = 10.5 Hz, COCH 2, 1 H). 13C NMR (126 MHz, CDCl3): δ = 170.7 (C=O), 168.3 (C=N), 146.5 (ArC), 143.3 (ArC), 140.7 (ArC), 138.6 (ArC), 131.3 (ArC), 130.7 (ArC), 130.3 (ArC), 129.6 (ArC × 2), 129.3 (ArC × 2), 128.4 (ArC × 2), 128.3 (ArC × 2), 127.5 (ArC), 124.7 (ArC), 124.2 (ArC), 57.2 (COCH2). ESI-HRMS: m/z calcd for C21H16N2O [+H]+: 313.1335; found: 313.1338. LC–MS purity (UV) = 90%, t R = 16.10 min.1-(4-Nitrophenyl)-3-(4-nitrophenyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (7)The product was obtained as white solid (0.60 mmol scale, 2 equiv of diaryliodonium triflate, 146 mg, 51%). 1H NMR (500 MHz, CDCl3): δ = 8.34–8.22 (m, ArH, 4 H), 7.85–7.79 (m, ArH, 2 H), 7.77–7.71 (m, ArH, 2 H), 7.74–7.57 (m, ArH, 3 H), 7.59–7.50 (m, ArH, 3 H), 7.41–7.32 (m, ArH, 2 H), 7.07–7.02 (m, ArH, 1 H). 13C NMR (126 MHz, CDCl3): δ = 166.0 (C=O), 158.3 (C=N), 149.1 (ArC), 146.7 (ArC), 145.6 (ArC), 144.1 (ArC), 143.3 (ArC), 135.0 (ArC), 132.6 (ArC), 131.5 (ArC), 129.9 (ArC), 129.6 (ArC), 129.5 (ArC × 2), 128.9 (ArC × 2), 126.8 (ArC × 2), 126.3 (ArC), 125.4 (ArC) 124.5 (ArC × 2), 124.3 (ArC × 2), 121.3 (ArC × 2). ESI-HRMS: m/z calcd for C26H17N5O5 [+H]+: 480.1230; found: 480.1245. LC–MS purity (UV) = 95%, t R = 18.35 min.1,1′-Oxybis(4-nitrobenzene)To a solution of (4-nitrophenyl)phenyliodonium triflate (30 mg, 0.06 mmol) in DCE (1 mL) was added sodium hydroxide (aq., 1 mL) and stirred for 20 min at room temperature. Upon completion, the reaction was diluted with dichloromethane (5 mL × 3) and the layers were separated. Combined organic layers were dried (MgSO4) and concentrated under reduced pressure to afford the product as a white powder (7 mg, 43%). 1H NMR (500 MHz, CDCl3): δ = 8.33–8.27 (m, ArH, 4 H), 7.19–7.14 (m, ArH, 4 H).13C NMR (126 MHz, CDCl3): δ = 160.6 (ArC × 2), 144.2 (ArC × 2), 126.2 (ArC × 4), 119.3 (ArC × 4). ESI-HRMS: m/z calcd for C12H8N2O5 [+H]+: 261.0511; found: 261.0513.
  • 43 CCDC numbers 1560492–1560494 contain the supplementary crystallographic data for compounds 3a, 3h, 3i. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.