FLUORINATED DERIVATIVES OF METHOXYDIBENZO[B,F]OXEPIN AND METHOD FOR OBTAINING THEREOF

Abstract

The invention provides fluorinated derivatives of methoxydibenzo[b,f]oxepin of general formula (1) and general formula (2) and a method for obtaining thereof in a catalysed reaction of fluoroazobenzene with methoxydibenzo[b,f]oxepin. The preferable catalyst of the reaction is triethylamine, and the compounds obtained may be useful as molecular switches in biological systems and photopharmacology.

Claims

1. A fluorine derivative of methoxydibenzo[b,f]oxepin of general formula (1) and general formula (2): ##STR00002## wherein: R.sup.1, R.sup.2=H or OMe; and R.sup.3, R.sup.4, R.sup.5=H or F.

2. A method for obtaining the fluorine derivative as defined in claim 1, wherein the method comprises a reaction of a methoxydibenzo[b,f]oxepin of general formula (3): ##STR00003## wherein: R.sup.1, R.sup.2=H or OMe; with a fluoroazobenzene selected from the group of compounds of general formula (4) or (5): ##STR00004## wherein: R.sup.3, R.sup.4, R.sup.5=H or F; in a solvent in the presence of a catalyst, comprising the following steps: a) thionyl chloride is added to fluoroazobenzene, and thereafter the mixture is heated; b) the reaction mixture is evaporated to dryness, then dissolved several times in an aprotic organic solvent and evaporated to dryness; c) methoxydibenzo[b,f]oxepin is dissolved in an aprotic organic solvent, a catalyst is added, and the residue from step (b) is dissolved in the aprotic organic solvent; and d) the reaction mixture is stirred.

3. The method according to claim 2, wherein the ratio of fluorobenzene to thionyl chloride in step (a) is 1:50 mol/mol.

4. The method according to claim 2, wherein the reaction mixture in step (a) is heated to 80 C. for 30 min.

5. The method according to claim 2, wherein the aprotic organic solvent in step (b) is methylene chloride.

6. The method according to claim 2, wherein the aprotic organic solvent in step (c) is ethyl acetate.

7. The method according to claim 2, wherein the catalyst in step (c) is triethylamine.

8. The method according to claim 2, wherein the ratio of fluoroazobenzene to methoxydibenzo[b,f]oxepin is 1:1 mol/mol, preferably 1:0.85 mol/mol.

9. The method according to claim 7, wherein the catalyst in step (c) is used in a ratio of 25:1 mol/mol relative to fluoroazobenzene.

10. The method according to claim 2, wherein the reaction mixture in step (d) is stirred at 25 C. for 1 h to 24 h.

Description

DESCRIPTION OF THE FIGURES

[0021] FIG. 1 shows fluoroazo derivatives of methoxydibenzo[b,f]oxepin of general formula (1) obtained by the method according to the invention.

[0022] FIG. 2 shows fluoroazo derivatives of methoxydibenzo[b,f]oxepin of general formula (2) obtained by the method according to the invention.

[0023] FIG. 3 shows the structure of methoxydibenzo[b,f]oxepin used to obtain azo derivatives of methoxydibenzo[b,f]oxepin in the method according to the invention.

[0024] FIG. 4 shows the general structure of fluoroazobenzene used as a substrate in the method for obtaining derivatives of general formula (1) according to the invention.

[0025] FIG. 5 shows the general structure of fluoroazobenzene used as a substrate in the method for obtaining derivatives of general formula (2) according to the invention.

[0026] The following examples illustrate the invention without limiting it.

IMPLEMENTATION EXAMPLE

General Procedure for the Production of Compounds 1a-1h and Compounds 2a-2h

[0027] In a 5 ml round-bottom flask, 0.2 mmol of the corresponding fluoroazobenzene (4a-d/5a-d) and a magnetic stirring element were placed. Then 50 equivalents of thionyl chloride were added. The whole mixture was heated at 80 C. under a reflux condenser for about 30 minutes. The reaction mixture was evaporated to dryness on a rotary evaporator. Approximately 2 ml of DCM was added and evaporated again to get rid of residual SOCl.sub.2. The operation was repeated twice. 0.85 equivalent of methoxydibenzo[b,f]oxepin (3a-b) was placed in a vial together with a magnetic stirring element and dissolved in 1 ml of ethyl acetate. The contents were stirred.

[0028] Then 0.25 mmol of triethylamine was added to the solution using an automatic pipette. The dry residue after evaporation of the thionyl chloride was dissolved in 1 ml of ethyl acetate and transferred to a vial with the contents being stirred. The system was closed with a stopper and the contents being stirred were left overnight.

[0029] After this time, the reaction mixture was analysed based on the position of the spots on a TLC plate in the hexane-ethyl acetate system at a volume ratio of 7:3. The mixture was evaporated and dissolved in a small amount of DCM and then purified on a chromatography column in the above system.

[0030] Sixteen derivatives (compounds of formulae 1a-h and 2a-h) were obtained as yellow-orange powders: [0031] Compound (1a): yield: 46%, mp=215.5 C. [0032] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.57 (1 H, s, NH), 7.79 (1 H, d, J.sub.H2,H4=1.5 Hz, H.sub.4), 7.66 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.27 (1 H, d, H.sub.1), 7.12-7.08 (2H, m, H.sub.7, H.sub.8), 6.83 (1 H, dd, J.sub.H8,H9=6.5 Hz, J.sub.H7,H9=3 Hz, H.sub.9), 6.78 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.72 (1 H, spin system AB, d, H.sub.11), 3.87 (3 H, s, OCH.sub.3); [0033] Azofluorobenzene ring: 8.18 (2 H, d, J.sub.H2.H3=8.5 Hz, H.sub.3), 8.02 (2 H, d, H.sub.2), 7.95 (2 H, dd, J.sub.H2,H3=8 Hz, J.sub.H2,H4=2 Hz, H.sub.2), 7.65-7.61 (3 H, m, H.sub.3, H.sub.4). [0034] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 164.75, 164.53, 156.62, 156.56, 156.26, 153.53, 153.49, 151.92, 151.48, 151.45, 144.20, 144.17, 140.85, 136.74, 132.71, 132.11, 131.48, 131.47, 129.68, 129.57, 129.25, 129.17, 129.14, 128.92, 128.77, 128.69, 128.61, 127.59, 126.09, 125.95, 125.09, 125.06, 122.79, 122.40, 120.54, 120.51, 120.02, 119.52, 116.63, 116.53, 113.25, 113.16, 113.00, 112.97, 56.16, 56.13 (duplicated signals from atropoisomers). [0035] HRMS (ESI): C.sub.28H.sub.21N.sub.3O.sup.3+, calculated m/z: 447.15774; found m/z: 447.15778. [0036] Compound (1b): yield: 76%, mp=242.5 C.

[0037] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.57 (1 H, s, NH), 7.78 (1 H, d, J.sub.H2.H4=2.5 Hz, H.sub.4), 7.66 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.27 (1 H, d, H.sub.1), 7.10-7.08 (2 H, m, H.sub.7, H.sub.8), 6.83 (1 H, dd, J.sub.H8.H9=6.5 Hz, J.sub.H7.H9=2.5 Hz, H.sub.9), 6.78 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.72 (1 H, AB spin system, d, H.sub.11), 3.87 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.18 (2 H, d, J.sub.H2,H3=8.5 Hz, H.sub.2), 8.03 (2 H, dd, J.sub.H2,H3=8.5 Hz, J.sub.H2,F=5 Hz, H.sub.2), 8.01 (2 H, d, H.sub.2), 7.47 (2 H, t, J.sub.H3,F=8.5 Hz, H.sub.3). [0038] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 165.15, 164.73, 163.15, 156.61, 156.09, 153.40, 151.47, 148.72, 148.70, 144.20, 140.84, 136.76, 131.48, 129.68, 129.25, 129.14, 128.77, 128.74, 128.70, 126.09, 125.26, 125.19, 125.09, 122.75, 122.68, 122.39, 120.54, 119.43, 116.68, 116.62, 116.54, 116.50, 115.95, 115.77, 113.24, 113.17, 113.00, 56.15 (duplicated signals from atropoisomers). [0039] HRMS (ESI): C.sub.28H.sub.20FN.sub.3O.sub.3.sup.+, calculated m/z: 465.14832; found m/z: 465.14843. [0040] Compound (1c): yield: 26%, mp=246 C. [0041] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.58 (1 H, s, NH), 7.78 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.66 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.27 (1 H, d, H.sub.1), 7.09 (1 H, t, J.sub.H8,H9,7=6.5 Hz, H.sub.8), 7.08 (1 H, dd, J.sub.H7,H9=2.5 Hz, H.sub.7), 6.83 (1 H, dd, H.sub.9), 6.78 (1 H, AB spin system, d, J.sub.H10.H11=11.5 Hz, H.sub.10), 6.72 (1 H, AB spin system, d, H.sub.11), 3.87 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.18 (2 H, d, J.sub.H2,H3=8.5 Hz, H.sub.3), 8.01 (2 H, d, H.sub.2), 7.87 (1 H, td, J.sub.H5,H6=9 Hz, J.sub.H5,F=6.5 Hz H.sub.6), 7.62 (1 H, ddd, J.sub.H3,F=9 Hz, J.sub.H3,H5=3 Hz, H.sub.3), 7.32-7.30 (1 H, m, H.sub.5). [0042] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 164.69, 164.45, 156.61, 156.56, 156.10, 153.54, 151.47, 151.45, 144.19, 144.17, 140.81, 140.79, 137.16, 133.73, 131.48, 131.47, 129.68, 129.66, 129.25, 129.21, 129.19, 128.78, 128.72, 126.12, 126.01, 125.09, 125.07, 122.61, 120.54, 120.52, 119.34, 119.25, 119.09, 116.64, 116.55, 113.25, 113.18, 113.00, 112.98, 112.79, 112.60, 105.97, 105.76, 105.57, 56.15, 56.13 (duplicated signals from atropoisomers). [0043] HRMS (ESI): C.sub.28H.sub.19F.sub.2N.sub.3O.sub.3.sup.+, calculated m/z: 483.13890; found m/z: 483.13884. [0044] Compound (1d): yield: 16%, mp=230 C. .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.59 (1 H, s, NH), 7.78 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.65 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.27 (1 H, d, H.sub.1), 7.08 (1 H, t, J.sub.H8,H7,9=6 Hz, H.sub.8), 7.07 (1 H, dd, J.sub.H7,H9=3 Hz, H.sub.7), 6.82 (1 H, dd, H.sub.9), 6.77 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.71 (1 H, AB spin system, d, H.sub.11), 3.86 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.19 (2 H, d, J.sub.H2,H3=8.5 Hz, H.sub.3), 7.99 (2 H, d, H.sub.2), 7.61 (1 H, tt, J.sub.H3,H4=8.5 Hz, J.sub.H4,F=6 Hz, H.sub.4), 7.36 (2 H, t, J.sub.H3,F=9.5 Hz, H.sub.3). [0045] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 164.62, 164.39, 156.62, 156.56, 156.44, 155.96, 154.00, 153.90, 151.48, 151.45, 144.20, 144.17, 140.78, 140.76, 137.59, 134.61, 132.59, 131.48, 131.47, 130.23, 129.68, 129.66, 129.26, 129.24, 129.19, 128.87, 128.80, 128.74, 126.16, 126.05, 125.10, 125.07, 122.41, 120.54, 120.52, 118.25, 116.66, 116.56, 113.27, 113.25, 113.19, 113.09, 113.01, 112.98, 112.55, 112.37, 56.16, 56.13 (duplicated signals from atropoisomers). [0046] HRMS (ESI): C.sub.28H.sub.19F.sub.2N.sub.3O.sub.3.sup.+, calculated m/z: 483.13890; found m/z: 483.13901. [0047] Compound (1e): yield: 30%, mp=168 C. [0048] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.55 (s, .sup.1H, NH), 7.79 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.56 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.23 (1 H, d, H.sub.1), 7.18 (1 H, d, J.sub.H8,H9=8.5 Hz, 6.80 (1 H, d, J.sub.H6,H8=2.5 Hz, H.sub.6), 6.77 (1 H, dd, H.sub.8), 6.64 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.59 (1 H, AB spin system, d, H.sub.11), 3.78 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.18 (2 H, d, J.sub.H2,H2=8.5 Hz, H.sub.2), 8.02 (2 H, d, H.sub.3), 7.95 (2 H, dd, J.sub.H2,H3=8.5 Hz, J.sub.H2,H4=2 Hz, H.sub.2), 7.63-7.62 (3 H, m, H.sub.3, H.sub.4). [0049] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 164.69, 161.18, 157.31, 156.07, 153.55, 151.92, 140.62, 136.71, 132.11, 130.20, 129.57, 129.30, 129.08, 128.55, 127.20, 126.02, 122.92, 122.79, 122.43, 116.84, 112.97, 111.22, 106.68, 55.52. [0050] HRMS (ESI): C.sub.28H.sub.21N.sub.3O.sub.3.sup.+, calculated m/z: 447.15774; found m/z: 447.15764. [0051] Compound (1f): yield: 34%, mp=218 C. [0052] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.55 (1 H, s, NH), 7.79 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.56 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.23 (1 H, d, H.sub.1), 7.18 (1 H, d, J.sub.H8,H9=8.5 Hz, H.sub.9), 6.80 (1 H, d, J.sub.H6,H8=2.5 Hz, H.sub.6), 6.77 (1 H, dd, H.sub.8), 6.64 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.59 (1 H, AB spin system, d, H.sub.11), 3.78 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.17 (2 H, d, J.sub.H2,H3=8.5 Hz, H.sub.3), 8.02 (2 H, dd, J.sub.H2,H3=9 Hz, J.sub.H2,F =5 Hz, H.sub.2), 8.01 (2 H, d, H.sub.2), 7.47 (2 H, t, J.sub.H3,F=9 Hz, H.sub.3). [0053] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 165.16, 164.67, 164.44, 163.16, 161.18, 161.15, 157.31, 157.28, 156.11, 156.07, 156.02, 153.42, 149.66, 149.64, 148.72, 148.69, 140.61, 140.50, 136.73, 136.68, 132.77, 130.20, 130.18, 129.30, 129.23, 129.08, 128.68, 128.55, 128.47, 127.20, 126.03, 125.89, 125.27, 125.20, 122.92, 122.75, 122.68, 122.43, 119.47, 116.84, 116.74, 116.69, 116.50, 115.95, 115.77, 112.97, 112.87, 111.21, 111.18, 106.68, 106.66, 55.52, 55.50 (duplicated signals from atropoisomers). [0054] HRMS (ESI): C.sub.28H.sub.20FN.sub.3O.sub.3+, calculated m/z: 465.14832; found m/z: 465.14824. [0055] Compound (1g): yield: 23%, mp=215 C. [0056] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.57 (1 H, s, NH), 7.79 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.56 (1 H, dd, J.sub.H1,H2=8 Hz, H.sub.2), 7.23 (1 H, d, H.sub.1), 7.18 (1 H, d, J.sub.H8,H9=8.5 Hz, H.sub.9), 6.80 (1 H, d, J.sub.H6,H8=2.5 Hz, H.sub.6), 6.77 (1 H, dd, H.sub.8), 6.64 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.59 (1 H, AB spin system, d, H.sub.11), 3.78 (3 H, s, OCH.sub.3); Azofluorobenzene ring 8.18 (2 H, d, J.sub.H2,H3=8.5 Hz, H.sub.3), 8.01 (2 H, d, H.sub.2), 7.87 (1 H, td, J.sub.H5,H6=8.5 Hz, J.sub.H6,F=6.5 Hz, H.sub.6), 7.62 (1 H, ddd, J.sub.H3,F=9 Hz, J.sub.H3,H5=2.5 Hz, H.sub.3), 7.31-7.27 (1 H, m, H.sub.5). [0057] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 164.63, 161.19, 157.30, 157.28, 156.06, 153.58, 153.55, 140.58, 137.13, 130.20, 129.31, 129.24, 129.15, 128.67, 128.56, 127.20, 126.06, 125.94, 122.92, 122.65, 119.33, 119.25, 119.13, 116.85, 116.76, 112.99, 112.82, 112.63, 111.22, 106.68, 106.66, 105.98, 105.79, 105.57, 55.52, 55.51 (duplicated signals from atropoisomers). [0058] HRMS (ESI): C.sub.28H.sub.19F.sub.2N.sub.3O.sub.3.sup.+, calculated m/z: 483.13890; found m/z: 483.13864. [0059] Compound (1h): yield: 39%, mp=175 C. [0060] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.58 (1 H, s, NH), 7.79 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.56 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.23 (1 H, d, H.sub.1), 7.18 (1 H, d, J.sub.H8,H9=8.5 Hz, H.sub.9), 6.80 (1 H, d, J.sub.H6,H8=2.5 Hz, H.sub.6), 6.77 (1 H, dd, H.sub.8), 6.64 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.59 (1 H, AB spin system, d, H.sub.11), 3.78 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.19 (2 H, d, J.sub.H2,H3=8.5 Hz, H.sub.3), 8.00 (2 H, d, H.sub.2), 7.62 (1 H, tt, J.sub.H3,H4=8.5 Hz, J.sub.H4,F=6 Hz, H.sub.4), 7.37 (2 H, t, J.sub.H3,F=9 Hz, H.sub.3). [0061] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 164.55, 164.31, 161.19, 161.16, 157.31, 157.28, 156.44, 156.06, 156.01, 155.95, 154.00, 153.93, 150.91, 148.93, 140.55, 137.55, 134.57, 132.58, 130.20, 130.18, 129.31, 129.24, 129.18, 128.81, 128.57, 128.51, 127.19, 126.09, 125.97, 122.91, 122.90, 122.44, 118.29, 116.87, 116.75, 113.27, 113.24, 113.11, 113.09, 113.01, 112.89, 112.39, 111.22, 111.18, 106.68, 106.66, 55.52, 55.50 (duplicated signals from atropoisomers). [0062] HRMS (ESI): C.sub.28H.sub.19F.sub.2N.sub.3O.sub.3.sup.+, calculated m/z: 483.13890; found m/z: 483.13899. [0063] Compound (2a): yield: 53%, mp=175 C. .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.62 (1 H, s, NH), 7.79 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.67 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.28 (1 H, d, H.sub.1), 7.09 (1 H, t, J.sub.H8,H7,9=6.5 Hz, H.sub.8), 7.08 (1 H, dd, J.sub.H7,H9=2 Hz, H.sub.7), 6.83 (1 H, dd, H.sub.9), 6.78 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.72 (1 H, AB spin system, d, H.sub.11), 3.87 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.47 (1 H, t, J.sub.H2,H4,6=2 Hz, H.sub.2), 8.15 (1 H, ddd, J.sub.H5,H6=8 Hz, J.sub.H4,H6=1 Hz, H.sub.6), 8.10 (1 H, ddd, J.sub.H4,H5=8 Hz, H.sub.4), 7.95 (2 H, dd, J.sub.H2,H3=8.5 Hz, J.sub.H2,H4=1.5 Hz, H.sub.2), 7.77 (1 H, t, H.sub.5), 7.66-7.61 (3 H, m, H.sub.3, H.sub.4). [0064] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 164.79, 164.52, 156.62, 156.60, 153.57, 153.32, 151.85, 151.77, 151.48, 151.45, 144.21, 144.19, 140.84, 140.72, 135.97, 135.29, 131.93, 131.48, 131.46, 130.59, 129.73, 129.69, 129.66, 129.58, 129.25, 128.95, 128.92, 128.77, 127.49, 126.39, 126.09, 126.07, 125.37, 125.09, 122.69, 122.05, 121.82, 120.55, 120.02, 119.93, 116.65, 116.54, 113.27, 113.14, 113.01, 56.16, 56.15 (duplicated signals from atropoisomers). [0065] HRMS (ESI): C.sub.28H.sub.21N.sub.3O.sub.3H.sup.+, calculated m/z: 448.16557; found m/z: 448.16562. [0066] Compound (2b): yield: 23%, mp=168.5 C. [0067] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f] oxepin ring: 10.62 (1 H, s, NH), 7.79 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.66 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.27 (1 H, d, H.sub.1), 7.12-7.08 (2 H, m, H.sub.7, H.sub.8), 6.83 (1 H, dd, J.sub.H8,H9=6 Hz, J.sub.H7,H9=3 Hz, H.sub.9), 6.78 (1 H, AB spin system, d, J.sub.H10,H11=11 Hz, H.sub.10), 6.72 (1 H, AB spin system, d, H.sub.11), 3.87 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.46 (1 H, t, J.sub.H2,H4,6 =1.5 Hz, H.sub.2), 8.16-8.14 (1 H, m, H.sub.6), 8.10-8.08 (1 H, m, H.sub.4), 8.03 (2 H, dd, J.sub.H2,H3=8.5 Hz, J.sub.H2,F=5 Hz, H.sub.2), 7.76 (1 H, t, J.sub.H5,H4,6 =8 Hz, H.sub.5), 7.47 (2 H, t, J.sub.H3,F=8.5 Hz, H.sub.3). [0068] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 165.05, 164.77, 164.51, 163.06, 156.62, 156.60, 153.45, 151.65, 151.48, 151.46, 149.50, 149.47, 148.64, 148.61, 144.21, 140.83, 140.71, 135.98, 135.42, 131.48, 131.46, 130.60, 129.73, 129.69, 129.66, 129.25, 129.07, 128.77, 126.47, 126.09, 125.39, 125.15, 125.09, 125.07, 122.76, 122.69, 121.80, 120.55, 119.92, 116.68, 116.65, 116.55, 116.49, 115.95, 115.77, 113.26, 113.16, 113.01, 56.16, 56.15 (duplicated signals from atropoisomers). [0069] HRMS (ESI): C.sub.28H.sub.20FN.sub.3O.sub.3H.sup.+, calculated m/z: 466.15615; found m/z: 466.15591. [0070] Compound (2c): yield: 87%, mp=190.5 C. [0071] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.63 (1 H, s, NH), 7.78 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.66 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.27 (1 H, d, H.sub.1), 7.10-7.09 (2 H, m, H.sub.7,H.sub.8), 6.83 (1 H, dd, J.sub.H8,H9=6.5 Hz, J.sub.H7,H9=3 Hz, H.sub.9), 6.77 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.72 (1 H, AB spin system, d, H.sub.11), 3.87 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.46 (1 H, t, J.sub.H2,H4,6 =2 Hz, H.sub.2), 8.17 (1 H, ddd, J.sub.H5,H6=8 Hz, J.sub.H4,H6=1 Hz, H.sub.6), 8.09 (1 H, ddd, J.sub.H4,H5=8 Hz, H.sub.4), 7.88 (1 H, td, J.sub.H5,H6=8.5 Hz, J.sub.H6,F=6.5 Hz, H.sub.6), 7.77 (1 H, t, H.sub.5), 7.62 (1 H, ddd, J.sub.H3,F=9 Hz, J.sub.H3,H5=2.5 Hz, H.sub.3), 7.31-7.27 (1 H, m, H.sub.5.). [0072] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 165.46, 164.68, 164.29, 163.45, 161.01, 158.95, 156.61, 156.59, 153.68, 151.84, 151.47, 151.45, 144.20, 144.18, 140.80, 140.66, 136.91, 136.04, 135.37, 131.48, 131.46, 131.01, 129.81, 129.68, 129.65, 129.25, 129.12, 128.78, 127.34, 126.12, 125.30, 125.09, 123.36, 122.27, 121.52, 120.54, 119.38, 116.65, 116.58, 113.27, 113.19, 113.00, 112.63, 112.10, 105.96, 105.75, 105.56, 105.19, 105.00, 104.79, 56.15 (duplicated signals from atropoisomers). [0073] HRMS (ESI): C.sub.28H.sub.19F.sub.2N.sub.3O.sub.3H.sub.+, calculated m/z: 484.14672; found m/z: 484.14652. [0074] Compound (2d): yield: 36%, mp=179.5 C. [0075] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.64 (1 H, s, NH), 7.78 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.66 (1 H, dd, J.sub.H1,H2=8.5 Hz, Hz), 7.27 (1 H, d, H.sub.1), 7.10-7.08 (2 H, m, H.sub.7,H.sub.8), 6.83 (1 H, dd, J.sub.H8.H9=6.5 Hz, J.sub.H7,H9=3 Hz, H.sub.9), 6.78 (1 H, AB spin system, d, J.sub.H10.H11=11.5 Hz, H.sub.10), 6.72 (1 H, AB spin system, d, H.sub.11), 3.87 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.46 (1 H, t, J.sub.H2,H4,=2 Hz, H.sub.2), 8.21 (1 H, ddd, J.sub.H5,H6=8 Hz, J.sub.H4,H6=1.5 Hz, J.sub.H2,H6=1 Hz, H.sub.6), 8.07 (1 H, ddd, J.sub.H4,H5=8 Hz, J.sub.H2,H4=1 Hz, H.sub.4), 7.79 (1 H, t, H.sub.5), 7.61-7.59 (1 H, m, H.sub.4), 7.37 (2 H, t, J.sub.H3,H4=9 Hz, J.sub.H3,F=9 Hz, H.sub.3). [0076] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 164.56, 164.06, 156.58, 155.94, 154.17, 153.89, 152.34, 151.48, 151.45, 150.97, 149.00, 146.02, 144.21, 144.19, 140.78, 140.70, 140.60, 136.06, 135.38, 132.34, 131.61, 131.45, 130.26, 130.19, 130.11, 129.91, 129.68, 129.65, 129.35, 129.26, 128.83, 128.80, 128.19, 126.17, 126.14, 125.10, 124.96, 122.14, 121.02, 120.55, 118.36, 116.68, 116.61, 113.30, 113.24, 113.21, 113.01, 112.51, 56.16 (duplicated signals from atropoisomers). [0077] HRMS (ESI): C.sub.28H.sub.19F.sub.2N.sub.3O.sub.3H.sup.+, calculated m/z: 484.14672; found m/z: 484.14667. [0078] Compound (2e): yield: 80%, mp=193.5 C. [0079] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.61 (1 H, s, NH), 7.80 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.57 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.23 (1 H, d, H.sub.1), 7.18 (1 H, d, J.sub.H8,H9=8.5 Hz, H.sub.9), 6.80 (1 H, d, J.sub.H6,H8=2.5 Hz, H.sub.6), 6.77 (1 H, dd, H.sub.8), 6.64 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.59 (1 H, AB spin system, d, H.sub.11), 3.78 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.47 (1 H, t, J.sub.H2,H4,6=2 Hz, H.sub.2), 8.15 (1 H, ddd, J.sub.H5,H6=8 Hz, J.sub.H4,H6=1 Hz, H.sub.6), 8.10 (1 H, ddd, J.sub.H4,H5=8 Hz, H.sub.4), 7.95 (2 H, dd, J.sub.H2,H3=8.5 Hz, J.sub.H2,H4=1.5 Hz, H.sub.2), 7.77 (1 H, t, H.sub.5), 7.65-7.60 (3 H, m, H.sub.3, H.sub.4). [0080] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 164.72, 164.44, 161.18, 157.31, 157.29, 156.06, 156.04, 153.59, 153.32, 151.84, 151.79, 140.62, 140.49, 135.94, 135.24, 131.94, 130.55, 130.20, 129.77, 129.58, 129.30, 129.28, 129.00, 128.93, 128.54, 127.50, 127.21, 127.17, 126.32, 126.02, 125.37, 122.93, 122.90, 122.69, 122.18, 121.77, 120.00, 119.78, 116.85, 116.72, 113.00, 112.86, 111.22, 106.68, 106.66, 55.52 (duplicated signals from atropoisomers). [0081] HRMS (ESI): C.sub.28H.sub.21N.sub.3O.sub.3.sup.+, calculated m/z: 447.15774; found m/z: 447.15789. [0082] Compound (2f): yield: 62%, mp=188.5 C. [0083] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f] oxepin ring: 10.61 (1 H, s, NH), 7.79 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.57 (1 H, dd, J.sub.H1,H2=8 Hz, H.sub.2), 7.23 (1 H, d, H.sub.1), 7.18 (1 H, d, J.sub.H8,H9=8.5 Hz, H.sub.9), 6.80 (1 H, d, J.sub.H6,H8=2.5 Hz, H.sub.6), 6.77 (1 H, dd, H.sub.8), 6.64 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.59 (1 H, AB spin system, d, H.sub.11), 3.78 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.46 (1 H, t, J.sub.H2,H4,6=1.5 Hz, H.sub.2), 8.14 (1 H, ddd, J.sub.H5,H6=8 Hz, J.sub.H4,H6=1 Hz, H.sub.6), 8.09 (1 H, ddd, J.sub.H4,H5=8 Hz, H.sub.4), 8.03 (2 H, dd, J.sub.H2,H3=9 Hz, J.sub.H3,F=5 Hz, H.sub.2), 7.77 (1 H, t, H.sub.5), 7.47 (2 H, t, J.sub.H3,F=9 Hz, H.sub.3). [0084] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 165.05, 164.70, 164.42, 163.05, 161.64, 161.18, 159.68, 157.31, 157.29, 156.06, 156.04, 153.46, 151.66, 149.49, 149.47, 148.63, 148.60, 140.61, 140.48, 135.95, 135.37, 130.55, 130.20, 129.77, 129.29, 129.12, 128.54, 127.20, 127.17, 126.40, 126.02, 126.00, 125.38, 125.14, 125.07, 122.92, 122.90, 122.74, 122.67, 121.96, 121.76, 119.76, 116.84, 116.73, 116.67, 116.49, 115.95, 115.77, 112.99, 112.88, 111.21, 106.68, 106.66, 55.51, 54.89 (duplicated signals from atropoisomers). [0085] HRMS (ESI): C.sub.28H.sub.20FN.sub.3O.sub.3.sup.+, calculated m/z: 465.14832; found m/z: 465.14853. [0086] Compound (2g): yield: 89%, mp=169.5 C. [0087] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.61 (1 H, s, NH), 7.79 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.56 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.23 (1 H, d, H.sub.1), 7.18 (1 H, d, J.sub.H8,H9=8.5 Hz, H.sub.9), 6.80 (1 H, d, J.sub.H6,H8=2.5 Hz, H.sub.6), 6.77 (1 H, dd, H.sub.8), 6.64 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.59 (1 H, AB spin system, d, H.sub.11), 3.78 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.46 (1 H, t, J.sub.H2,H4,6=2 Hz, H.sub.2), 8.17 (1 H, ddd, J.sub.H5,H6=8 Hz, J.sub.H4,H6=1 Hz, H.sub.6), 8.09 (1 H, ddd, J.sub.H4,H5=8 Hz, H.sub.4), 7.87 (1 H, td, J.sub.H5,H6=8.5 Hz, J.sub.H6,F=6 Hz, H.sub.6), 7.78 (1 H, t, H.sub.5), 7.62 (1 H, ddd, J.sub.H3,F=9 Hz, J.sub.H3,H5=2.5 Hz, H.sub.3), 7.27-7.31 (1 H, m, H.sub.5). [0088] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 165.37, 164.62, 164.21, 163.45, 161.18, 161.01, 158.95, 157.31, 157.29, 156.06, 156.04, 153.71, 151.86, 140.57, 140.43, 136.92, 136.02, 135.33, 130.95, 130.20, 129.85, 129.30, 129.28, 129.17, 128.55, 127.26, 127.19, 127.16, 126.05, 125.31, 123.38, 122.92, 122.89, 122.22, 121.66, 119.37, 119.29, 116.86, 116.77, 113.01, 112.92, 112.62, 112.11, 111.22, 106.68, 105.96, 105.77, 105.56, 105.19, 105.00, 104.79, 55.51 (duplicated signals from atropoisomers). [0089] HRMS (ESI): C.sub.28H.sub.19F.sub.2N.sub.3O.sub.3.sup.+, calculated m/z: 483.13890; found m/z: 483.13893. [0090] Compound (2h): yield: 91%, mp=167.5 C. [0091] .sup.1H NMR (500 MHz, DMSO-d.sub.6, 298K): (ppm): Dibenzo[b,f]oxepin ring: 10.63 (1 H, s, NH), 7.79 (1 H, d, J.sub.H2,H4=2 Hz, H.sub.4), 7.57 (1 H, dd, J.sub.H1,H2=8.5 Hz, H.sub.2), 7.23 (1 H, d, H.sub.1), 7.18 (1 H, d, J.sub.H8,H9=8.5 Hz, H.sub.9), 6.80 (1 H, d, J.sub.H6,H8=2.5 Hz, H.sub.6), 6.76 (1 H, dd, H.sub.8), 6.64 (1 H, AB spin system, d, J.sub.H10,H11=11.5 Hz, H.sub.10), 6.59 (1 H, AB spin system, d, H.sub.11), 3.78 (3 H, s, OCH.sub.3); Azofluorobenzene ring: 8.46 (1 H, t, J.sub.H2,H4,6=1.5 Hz, H.sub.2), 8.20 (1 H, ddd, J.sub.H5,H6=8 Hz, J.sub.H4,H6=1 Hz, H.sub.6), 8.07 (1 H, ddd, J.sub.H4,H5=8 Hz, H.sub.4), 7.79 (1 H, t, H.sub.5), 7.61 (1 H, tt, J.sub.H3,H4=8.5 Hz, J.sub.H4,F=6 Hz, H.sub.4), 7.37 (2 H, t, J.sub.H3,F=9 Hz, H.sub.3). [0092] .sup.13C NMR (125 MHz, DMSO-d.sub.6, 298K): (ppm): 164.49, 163.98, 161.18, 157.31, 157.29, 156.06, 156.03, 154.21, 153.85, 152.35, 150.91, 148.98, 140.56, 140.37, 136.03, 135.33, 132.35, 131.55, 130.19, 129.94, 129.38, 129.29, 129.28, 128.59, 128.56, 128.09, 127.19, 127.15, 126.10, 126.07, 124.96, 122.92, 122.89, 122.09, 121.13, 118.21, 116.88, 116.80, 113.23, 113.04, 112.94, 112.50, 111.23, 106.68, 55.52 (duplicated signals from atropoisomers). [0093] HRMS (ESI): C.sub.28H.sub.19F.sub.2N.sub.3O.sub.3H.sup.+, calculated m/z: 484.14672; found m/z: 484.14640.

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