Synthesis, crystal structures, and laser flash photolysis of 3-nitro-7a,15-methanonaphtho[1',2':6,7][1,3]oxazepino[3,2-a ]indole derivatives

The condensation of 1-substituted 9,9a-dihydro-1 H -imidazo[1,2-a ]indol-2(3 H )-ones with 2-hydroxy-6-nitro-1-naphthaldehyde afforded 1 ′ -carbamoylmethyl-8-nitrospiro[benzo[ f ]chromene-3,2 ′ -indole] derivatives, which underwent intramolecular cyclisation to derivatives of 3-nitro-7a,15-methanonaphtho[1 ′ ,2 ′ :6,7][1,3]oxazepino[3,2-a ]indole upon treatment with a strong base. Laser excitation of the obtained uncoloured molecules of trans - and cis -3-nitro-7a,15-methano-naphtho[1 ′ ,2 ′ :6,7][1,3]oxazepino[3,2-a ]indole induced the formation of short-lived photo-generated species, which absorb in the visible spectrum and thermally revert to the ground state on a nanosecond time scale.

The condensation of 1-substituted imidazo [ The assignments of trans/cis configurations to 6a-d and 7a-d were based on comparisons with 1 H NMR spectra of the most relevant compounds 16,28,29 and data from single-crystal X-ray analyses.For example, the 1 H NMR spectrum of 6a contained a singlet of 14-H at 4.47 ppm characteristic of the trans-diastereomer, while in the corresponding spectrum of 7a, the 14-H proton signal appeared as a doublet at 4.19 ppm ( 3 J 14,15 = 4.2 Hz), confirming the cisconfiguration of the molecule. 16,28 O To obtain unequivocal evidence for configuration of compounds trans-6a and cis-7a, we performed single-crystal X-ray analyses of these compounds.The molecule of trans-6a consists of indoline and 3,4-dihydro-2H-benzo[f]chromene structural units possessing common atoms with the central pyrrolidine ring (Figure 1, the crystallographic numbering does not represent the systematic numbering). 30The dihedral angle between the planes, in which the indole and 6-nitro-2-naphthol units are situated, is 110°.The pyrrolidine hydrogen atoms at C(12) and C( 13) are situated relative to the pyrrolidine ring plane in a mutual trans-disposition, while the dihedral angle H-C(12)-C(13)-H is 98.16°.The sum of the indoline nitrogen valence angles is 356.21° in trans-6a, indicating sp 2 -dominant hybridisation of the valence electrons (ca.88%).The N(1)-C(8) bond length is 1.395 Å and corresponds to the bond length of aniline derivatives possessing sp 2 hybridised nitrogens. 31The indoline nitrogen lone electron pair and the C(2)-O (15) bond are in the same plane.The amide group is in an s-Z-conformation.The benzylic phenyl ring and the indole moiety are situated in almost parallel planes.The asymmetric unit of cis-7a consists of the two independent crystallographic forms A and B of 7a and a molecule of the solvent, acetonitrile. 32Numbering of atoms is done only for form B for clarity, as the two structures are very similar, and the differences are minimal.The molecule of cis-7a involve the same structural units as the molecule trans-6a, but the dihedral angle between the planes in which the indoline and 3,4-dihydro-2H-benzo[f]chromene structural units are situated is ca.54° (Figure 2).The pyrrolidine hydrogen atoms at C(12b) and C(13b) are situated relative to the pyrrolidine ring main plane in a mutual cis-disposition, while the dihedral angle H-C(12b)-C(13b)-H is 33.8°.The sum of the indoline nitrogen valence angles is only 331.43° in cis-7a, indicating that the nitrogen atom is tetrahedral (91% sp 3 hybridisation).The C(8b)-N(1b) bond length is 1.432 Å, confirming the greater share of sp 3 hybridised electrons in the corresponding bond formation. 31The amide moiety is in an s-Z conformation, where the C=O bond is in the anti-position to the C(12b)-N(1b) bond.The acetonitrile molecule is held in the crystal by three hydrogen bonds connecting two crystallographically independent forms A and B. Due to the asymmetrical distribution of hydrogen bonds (one bond with form A and two bonds with form B), the molecules of cis-7a have some small differences in these crystallographically independent forms.The angle between the phenyl ring and naphthalene moiety, for example, is 62° in form A and 65° in form B.
The UV-Vis absorption spectra of 6a-d and 7a from solutions in acetonitrile were obtained at room temperature.As a representative example, the steady-absorption spectrum of trans-6a is shown in Figure 3 (black curve).It shows a strong absorption band at 360-380 nm that has been assigned to the 6-nitro-2-naphthoxy moiety and resembles the ground-state absorption of nitronaphtho [1,3]oxazine derivative 1, possessing a 4-nitro-1-naphthoxy moiety. 22The steadystate absorption spectra of compounds 6b-d and 7a were very similar (Table 1).When solutions of trans-6a-d in acetonitrile were treated with a two-fold excess of tetrabutylammonium hydroxide (TBAOH), a coloured product with an absorption maximum at 490-505 nm, characteristic of the 6-nitro-2-naphtholate chromophore, 22 was formed immediately (Table 1).As a representative example, the UV-Vis spectral behaviour of the compound trans-6a in acetonitrile after the addition of TBAOH is shown in Figure 3 (blue curve).However, adding a non-nucleophilic base, such as triethylamine, to a solution of trans-6a did not cause any absorption to appear in the visible part of the absorption spectrum (Figure 3, green curve).Therefore, the coloured form that appeared is presumably the adduct 8, formed via ring-opening and hydroxyl anion addition to the indole -carbon, as shown in Scheme 4. It is known that the formation of similar pseudo-bases occurred when 1,2,3,3-tetrasubstituted 3H-indolium salts are treated with alkali. 33,34It should be noted that the steady-state absorption spectrum of 2-hydroxy-6-nitronaphthaldehyde in acetonitrile exhibited absorption bands at 295 and 340 nm (Figure 4, black curve), while upon addition of TBAOH to the solution, a strong absorption band at 450 nm arose (Figure 4, blue curve) that indicates the formation of the corresponding nitronaphtholate anion.

Scheme 4.
Base and acid induced ring-opening reactions of trans-6a.   The 13 C NMR spectrum of compound trans-6a, registered in TFA-d, revealed signals that indicated the cleavage of the bicyclic ring system and the formation of the cation 9 (Scheme 4).Thus, a signal at 204.5 ppm was unambiguously assigned to the carbon of the C=N + group, while the signals of the remaining three carbon atoms of the pyrrolium ring were observed at 35.5 (CH 2 ), 43.1 (CH) and 71.1 (CH) ppm.When a large excess of TFA was added to a solution of trans-6a in acetonitrile,the UV-Vis spectrum revealed an absorption maximum at 335 nm (Figure 3, red curve), which was blue-shifted approximately 10 nm compared to the absorption maximum of trans-6a in pure acetonitrile and can be attributed to the 6-nitro-2-naphthol chromophore of the ring-open form 9. The transient absorption spectra of compounds trans-6a-d and cis-7a in acetonitrile were recorded in the nanosecond domain after UV-laser excitation and in all cases revealed absorption bands situated in the visible region of the electromagnetic spectrum (Table 2).As representative examples, the corresponding transient absorption spectra recorded for trans-6a and cis-7a are shown in Figures 5 and 6.In the case of compound trans-6a, the transient absorption band maximum was located at 440, with a shoulder at 505 nm, while in the case of compound cis-7a, the maximum was at 535 nm, with a shoulder at 440 nm.In both cases, the presence of absorption maxima in the visible region of the electromagnetic spectrum can presumably be attributed to the formation of zwitterionic forms 10 and 11, incorporating the 6nitro-2-naphtholate chromophore (Scheme 5).Kinetic traces monitored at a variety of wavelengths (Figure 7) indicated that the coloured species were formed during the excitation pulse (ca.6 ns).In all instances, the induced absorbance decays to zero as the ring-opened isomers trans-10 and cis-11 revert via thermal pathways to the original compounds trans-6a and cis-7a.Relaxation times, estimated from global fitting of the transient data (Table 2), revealed that the thermal reversion of trans-10 and cis-11 to the original form is fast and proceeds in nanosecond time scale.Similar results were obtained in the case of flash photolysis of compounds trans-6b-d.The quantum yields of the photochromic reactions were estimated using the molar extinction coefficients of the TBAOH-induced ring-opened forms (Table 1) obtained from the steady state absorption spectra measurements, as described elsewhere. 18The corresponding quantum yields of the investigated photochemical reactions were estimated to be ca.3.8-8.1% (Table 2).

Conclusions
New 7a,15-methanonaphtho[1′,2′:6,7][1,3]oxazepino[3,2-a]indole derivatives bearing an 8-nitro group were synthesised by the intramolecular cyclisation of 1′-carbamoylmethyl-8nitrospiro[benzo[f]chromene-3,2′-indole] derivatives upon treatment with a strong base.The relative trans/cis-configuration of the prepared bridged compounds was established by means of 1 H NMR spectroscopy and confirmed by single-crystal X-ray analysis.Their steady-state spectra in acetonitrile exhibited the main absorption band at approximately 370 nm, which is characteristic of the 6-nitro-2-naphthoxy chromophore.The addition of TBAOH to a solution of the aforementioned compounds in acetonitrile led to the ring-opening of the bridged system and generation of the 6-nitro-2-naphtholate chromophore with a  max of approximately 500 nm.UV laser excitation of the uncoloured molecules of trans-and cis-8-nitro-7a,15methanonaphtho[1′,2′:6,7][1,3]oxazepino[3,2-a]indole induces the formation of short-lived photogenerated species, presumably zwitterionic compounds, which absorb in the visible spectrum and thermally revert to the ground state on a nanosecond time scale.

Experimental Section
General.Reagents and solvents were purchased from Sigma-Aldrich and used without further purification.Reactions were monitored by TLC analysis on precoated silica gel plates (Kieselgel 60F 254 , Merck).Compounds were visualised with UV light or by treatment with iodine vapour.Column chromatography was performed on silica gel SI 60 (43-60 μm, E. Merck).Melting points were determined in open capillary tubes with a Büchi B-540 melting point apparatus.Infrared spectra were recorded on a Perkin Elmer Spectrum One spectrometer using potassium bromide pellets. 1 H NMR spectra were recorded at 300 MHz on a Varian Unity Inova spectrometer, at 400 MHz on a Bruker Avance III spectrometer. 13C NMR spectra were collected using the same instruments at 75, 100 and 175 MHz.The chemical shifts are expressed in ppm downfield relative to TMS, and the coupling constants (J), referring to apparent peak multiplicity, are reported in Hz.Diffraction data were collected on a Bruker-Nonius KappaCCD diffractometer at room temperature and at -100 °C.The crystal structures were solved using known programs. 35Elemental analyses were measured with a CE-440 elemental analyzer, Model 440 CHN/O/S.Low-resolution mass spectra were recorded via direct injection on a Waters Micromass ZQ 2000 mass spectrometer applying positive atmospheric pressure chemical ionization (APCI + , 20 V).High-resolution ESI-TOF mass spectra were measured on a Bruker maXis spectrometer.Steady state absorption spectra of the solutions were measured using a Shimadzu scanning spectrophotometer model UV-3101PC.Flash photolysis experiments were performed using a nanosecond Q-switched Nd:YAG laser (EKSPLA NL301), and pulses of the third harmonic (wavelength -355 nm, duration -6 ns) were applied for excitation. 19The energy of the pulses for flash photolysis was approximately 3.5 mJ.Sample transmission was probed using light flashes with a duration of ~100 μs generated by a laser-synchronised Xe lamp covering the spectral range of 380-850 nm.Temporal changes in the sample transmission were detected by two high-speed photodiodes (Thorlabs DET10A) placed behind two monochromators for the sample and reference beams.The signals were recorded using a 1 GHz bandwidth oscilloscope (Tektronix TDS7104).All nanosecond kinetic traces presented here were obtained by averaging at least 30 experimental measurements.To avoid local over-exposure of the sample, solutions were mixed with a home-built magnetic stirrer.IRF of the experiments was approximately 6 ns.Nanosecond-resolution flash-photolysis experimental data were analysed using global analysis techniques described elsewhere. 36All the flash-photolysis data presented here were fitted using a linear evolution model with the smallest number of compartments necessary to provide a satisfactory fit.One or two kinetic components were adequate to describe the data presented herein.The quantum yields of photochromic transformations were determined following the calibration method described elsewhere. 18Briefly, benzophenone was used as a standard with its intersystem crossing quantum yield assumed to be unity.The quantum yield of the photoinduced ring opening was determined with Equation 1: (1) The terms χ and χ bzP are the slopes of linear portions of the plots of the maximum amplitude of induced absorption measured at λ max against the pump pulse energy (A=f(E laser )) of the ringopened compound and benzophenone, respectively.The molar extinction coefficients ε of the investigated compounds were determined by chemically inducing the opening of the ring with TBAOH; ε bzP for its triplet absorption at 520 nm is 6.5 mM -1 cm -1 . 371,7,9,9,9a-Pentamethyl-9,9a-dihydro-1H-imidazo[1,2-a]indol-2(3H)-one (4d).7,9,9,9a-Tetramethyl-9,9a-dihydro-1H-imidazo[1,2-a]indol-2(3H)-one (3b) (2.61 g, 11.3 mmol) was dissolved in 25 ml DMF and finely powdered KOH (0.95 g, 16.95 mmol) was added.Iodomethane (4.81 g, 2.1 ml, 33.9 mmol) was added dropwise to the solution and the mixture was stirred for 2 h at rt.Then the reaction mixture was poured into water (100 ml) and extracted with ether (3 × 50 ml).The combined organic layer was dried over anhydrous Na 2 SO 4 , concentrated in vacuo and the residue was subjected to flash chromatography on silica gel (hexane/acetone 3:1) to yield the title compound 4d.Yellowish oil, yield 1.99 g (72%).IR: ν max 3035, 2968, 1704 cm -1 (C=O). 1 H NMR (400 MHz, CDCl 3 ): δ H 1.15 (3H, s, CH 3 ), 1.38 (3H, s, CH 3 ), 1.46 (3H, s, CH 3 ), 2.29 (3H, s, CH 3 ), 2.93 (3H, s, CH 3 ), 3.74 (1H, AB-d, J 15.6 Hz, CH), 4.00 (1H, AB-d, J 15.6 Hz, CHH′), 6.67 (1H, d, J 8.0 Hz, 5-H), 6.83 (1H, d, J 0.4 Hz, 8-H), 6.97 (1H, dd, J 8.0, 0.4 Hz, 6-H). 13C NMR (100 MHz, CDCl 3 ): δ C 21.2 (CH 3 ), 21.8 (CH 3 ), 24.2 (CH 3 ), 28.0 (CH 3 ), 28.3 (CH 3 ), 49.5 (C-9), 55.0 (CH 2 ), 92.6 (C-9a), 113.7 (CH), 122.9 (CH), 128.9 (CH), 131.9 (C), 140.

Figure 2 .
Figure 2. Ortep views of compound cis-7a: (a) view of the crystallographic forms A and B together with a molecule of acetonitrile; (b) view of hydrogen bonds in the asymmetric unit.

Figure 3 .
Figure 3. UV-Vis spectra of various forms of trans-6a in acetonitrile (black: 6a in pure acetonitrile, blue: chemically opened form of 6a with TBAOH, green: 6a with TEA, red: chemically opened form of 6a with TFA).

Figure 7 .
Figure 7. Transient absorption kinetics of 0.075 mM trans-6a in acetonitrile pumped with 355-nm light and probed at selected wavelengths.

Table 2 .
Summary of photochromic parameters of the investigated compounds heterolytic cleavage of the C-O bond to yield pyrrolo[1,2-a]indolium salts.