New Insight into the Photochromism of Spiropyrans: Substituent Effects on Equilibrium, Rate Constants, and Dipole Moments

Abstract

Spiropyrans (SPs) and merocyanines (MCs) are among the most widely used photochromic systems today. Besides solvent polarity and temperature, the electronic properties of the substituents have a significant influence on photochromic behavior. In this work, a comprehensive study on the influences of electron-donating and -withdrawing substituents at the benzopyran as well as the indole moiety of the photochromic system are elucidated. For this purpose, changes in rate constants and the shift of the SP/MC equilibrium are investigated utilizing UV/vis and NMR spectroscopy. Based on DFT calculations, a relationship between these properties and the dipole moments of the molecules is established.

Keywords

Spiropyran - Merocyanine - Photochromism - Substituent-effects - Rate constant - Dipole moment

The utilization of light as a dependable and readily available energy source has become an essential aspect in modern chemistry. Consequently, the interest in photoswitchable molecules has increased steadily over the past few decades. Today, a variety of these molecules is known, such as azobenzenes,[1] dithienylethenes,[2] Stenhouse adducts,[3] and spiropyrans (SPs).[4] Due to their different properties, they can be used for a wide variety of applications and research areas. These range from switchable materials[1a] [5] such as polymers, nanoparticles, and functionalized surfaces to biomedical applications[1b] [2c] [6] such as switchable fluorophores for labeling and imaging or the synthesis of switchable proteins. In this context, the structural motif of SPs has proven particularly useful, since it undergoes major structural and physical changes upon switching to the corresponding merocyanines (MCs) ([Fig. 1]). The photochromic properties of SPs were first reported in the 1950s by Hirshberg and Fisher.[6] Since then, numerous other types of stimuli such as metal ions,[4b] pH (acidochromism),[4a] [8] polarity of the solvent (solvato-chromism),[9] and mechanical force (mechanochromism)[10] have been discovered to influence the equilibrium between SPs and MCs, but these are not described further within this work.

Fig. 1 UV-mediated ring opening of a spiropyran (SP) to the corresponding merocyanine (MC). Ring closure can occur thermally as well as photochemically.

The SP scaffold offers high derivatization potential, and the photochromic properties of the system are highly affected not only by the type of substituents but also by their position ([Fig. 2]). While the derivatization of the indolium sidechain ([Fig. 2], green)[11] and at the benzopyran moiety ([Fig. 2], blue)[12] are already well studied, only limited information about the impact of substituents at the aromatic system of the indolium ([Fig. 2], red)[11a] [11b] [12c] is available.

Fig. 2 A subdivision of the general structure of indolium-based spiropyrans into four subunits.

Due to the use of different solvents and temperatures, available data are difficult to compare. Furthermore, the focus is often not on the influence on the photochromic properties of the system but on its properties as a photoacid. This is particularly common for the derivatization of the side chain.[11a] [12b]

This work elucidates the impact of derivatization at the benzopyran and indolium units of the system on its photochromic properties. Therefore, 19 SP/MC systems with electron-withdrawing (EWG) and electron-donating (EDG) substituents were synthesized. The kinetics of ring opening (SP ➔ MC, coloration) or ring closing (MC ➔ SP, discoloration) of the differently substituted systems were determined and compared via UV/vis spectroscopy. Additionally, the shift of the SP/MC equilibrium was studied using UV/vis and 1H NMR spectroscopy.

Synthesis of substituted SPs and MCs

Benzopyran-substituted SPs were synthesized either from Fisher base and the corresponding salicylic aldehyde using a procedure based on Roxburgh et al.[13] or from indolium iodide using triethylamine as base to scavenge the released HI ([Table 1]). In the absence of base, the free SP/MC is not isolated; instead, the corresponding HI adduct is obtained, which exhibits significantly different photochromic properties. Using either of both methods, SPs 1–13 featuring different patterns of bromo, nitro, and methoxy substituents were synthesized.

Table 1 Synthesis of benzopyran-substituted SP/MC systems 1–13

SP/MC	R	R′	Yield
1	H	H	93%a
2	Br	H	90%a
3	H	Br	93%a
4	Br	Br	68%b
5	NO2	H	83%a
6	H	NO2	81%a
7	NO2	Br	88%a
8	Br	NO2	78%b
9	NO2	NO2	66%a
10	NO2	OMe	45%a
11	OMe	NO2	38%a
12	OMe	H	98%a
13	H	OMe	69%a

^aSynthesized using method a.

^bsynthesized using method b.

Overall, the SPs could be obtained in high yields. In the case of compounds 10 and 11 containing an EWG group as well as an EDG group, the purification was difficult resulting in low yields. The yields obtained by method (b) were slightly lower, but purification was noticeably easier.

Additionally, systems 14–19 with different EWG or EDG at the indole moiety were synthesized ([Fig. 3]). For derivatives 14–17 with methoxy, carboxy, bromo, or methyl substituents, a Fisher indole synthesis was conducted starting from the corresponding substituted phenyl hydrazine hydrochlorides 20–23. Indoles 24–27 as well as the commercially available indoles 28 and 29 were then methylated to the derivatives 30–35 in very good yields. Only methylation of 29 was achieved with low yield since a variety of different methylation products were obtained. The final condensation step was conducted using Et₃N as base.

Fig. 3 Synthesis of indole-substituted SP/MC systems 14–19.

For UV/vis characterization, three measurements were performed for each derivative in methanol as solvent. One measurement each was carried out after irradiation with visible ([Fig. 4], green) and ultraviolet light ([Fig. 4], red). Prior to the third measurement, the samples were stored in the dark until thermal equilibrium between SP and MC had been reached ([Fig. 4], blue). Depending on the substituents, the time required for equilibration varies from seconds, minutes to hours or even several days.

Fig. 4 UV/vis-spectrum of SP/MC system 7 after irradiation with visible (green) or ultraviolet light (254 nm) (red) and after equilibration in the dark (blue). The spectra were obtained from 0.025 mm methanolic solutions.

UV/Vis Characterization of the Substituted SPs and MCs

UV/vis characterization via wavelength scans is exemplarily shown in [Fig. 4] for SP7. The spectra of all other derivatives can be found in the Supporting Information (SI, Scheme 1–25). The spectra obtained after irradiation with visible light resemble the SP form ([Fig. 4], green), only showing absorptions within the UV region. In the case of the example shown in [Fig. 4], a small absorption around 523 nm can be seen, which can be attributed to traces of MC. For all derivatives, an absorption band with a maximum between 320 and 400 nm as well as at least two absorption maxima below 300 nm are observed.

Upon irradiation with UV light ([Fig. 4], red), and therefore upon formation of the MC, the intensity of the absorption maxima below 300 nm is decreased (hypochromic shift), while the absorption at 320–400 nm shows a bathochromic and a hyperchromic shift. Additionally, a new absorption with a maximum between 500 and 570 nm is formed, being responsible for the characteristic color of the MCs. Once the sample is no longer exposed to light, the SP/MC ratio at the photo stationary state gradually shifts, resulting in the establishment of thermal equilibrium ([Fig. 4], blue).

The wavelength corresponds to the absorption maximum of the merocyanine, which was used for kinetic analysis. Entries highlighted in gray all show the same substitution pattern at the chrome unit. The molecules are sorted according to their rate constant from highest to lowest.

For compounds with strong EDG substituents (OMe) or only one weak EWG substituent (Br) at the benzopyran unit, the spectra at thermal equilibrium strongly resemble those after exposure to visible light, while for compounds with strong EWG substituents (NO₂), the spectrum at thermal equilibrium resembles the one at the photostationary state after irradiation with UV-light. This indicates increased stability of the MC form with increasing number and strength of EWG substituents at the benzopyran moiety. For 9, 14, and 17, the absorption of MC at thermal equilibrium even excited the absorption after irradiation with UV light. This already indicates high stabilization of the MC isomer.

To analyze the influence of the substituents on the photochromic properties of the different derivatives, rate constants for thermal decolorization (MC to SP) or thermal colorization (SP to MC) were determined via UV/vis-spectroscopy.[14] These are summarized in [Table 2] and sorted in descending order according to the observed rate constant.

Table 2 Rate constants for thermal stability of substituted SP/MC systems

SP/MC	R	R′	R″	λmax MC	k obs a = (k 1 + k 2)
1	H	H	H	554 nm	1.3 × 10−1
3	H	Br	H	555 nm	6.4 × 10−2
2	Br	H	H	561 nm	6.3 × 10−2
18	NO2	Br	NO2	559 nm	3.1 × 10−2
11	OMe	NO2	H	602 nm	3.0 × 10−2
4	Br	Br	H	566 nm	1.3 × 10−2
19	NO2	Br	NMe3I	544 nm	1.0 × 10−2
10	NO2	OMe	H	550 nm	1.4 × 10−3
6	H	NO2	H	543 nm	5.2 × 10−4
15	NO2	Br	COOH	541 nm	5.1 × 10−4
5	NO2	H	H	529 nm	1.1 × 10−4
8	Br	NO2	H	554 nm	8.3 × 10−5
16	NO2	Br	Br	532 nm	8.0 × 10−5
7	NO2	Br	H	523 nm	2.7 × 10−5
17	NO2	Br	Me	521 nm	1.9 × 10−5
14	NO2	Br	OMe	521 nm	1.7 × 10−5
9	NO2	NO2	H	507 nm	1.5 × 10−5

^a Measurements were conducted at 20 °C in 0.025 mM solutions of methanol.

When comparing rate constants and substitution patterns, clear trends can be seen: The highest rate constant of 0.13 s⁻¹ was obtained for the unsubstituted molecule 1. The addition of bromine substituents at the benzopyran (2–3) decreases the rate constant by up to one order of magnitude. Utilizing nitro groups as even stronger EWGs, the rate constants can be further decreased to 5.2 × 10⁻⁴ and 1.1 × 10⁻⁴ s⁻¹ for the monosubstituted derivative (5, 6). The addition of a second nitro substituent (9) leads to a further decrease by one order of magnitude to 1.5 × 10⁻⁵ s⁻¹. On the other hand, EDG groups like methoxy substituents show the opposite effect. This can be seen when comparing the nitro-substituted compounds 5 and 6 with derivatives 10 and 11, which contain one additional methoxy substituent. The methoxy group increases the rate constants from 1.1 × 10⁻⁴ to 1.4 × 10⁻³ s⁻¹ (5 ➔ 10) and from 5.2 × 10⁻⁴ to 3.0 × 10⁻² s⁻¹ (6 ➔ 11). For the SPs 12 and 13 with only a methoxy substituent at the benzopyran moiety, no photochromic isomerization can be detected at 20 °C (Δ < 0.005 a.u.). Only by decreasing the temperature, a very fast decoloration reaction can be observed.

Regarding the influence of the substituents at the indole unit, the opposite trend can be observed. While for compound 7 without any indole substituent, a rate constant of 2.7 × 10⁻⁵ s⁻¹ was determined, for the systems 14 and 17 with EDG substituents, the rate constants are decreased to 1.9 × 10⁻⁵ and 1.7 × 10⁻⁵ s⁻¹. EWG substituents (15, 16, 18 and 19) on the other hand lead to an increase of the rate constants. It can also be seen that not only the electronic character of the substituent has an impact but also the strength of its EDG or EWG character. Therefore, the bromine substituent of 16 leads only to a low increase of the rate constant while the highest increase was observed with an additional nitro substituent (18). A Hammett plot based on the rate constants of all indole-substituted derivatives is shown in [Fig. 5]. A linear correlation of the data can be observed, which would indicate a purely electronic influence of the substituents. Since the fit does not match perfectly, it could also be interpreted that the σ ≤ 0 and σ ≥ 0 regions are separated. This could indicate a change in the mechanism. It could be possible that systems with a strong push–pull effect tend to prefer the zwitterionic form of the MC, while those without this effect could prefer the neural quinoidal from. However, further investigations and additional data, especially for the σ ≤ 0 region, would be necessary for better interpretation. Details about the data points are reported in the SI (Scheme 43).

Fig. 5 Hammett plot of the thermal equilibration of indole-substituted compounds 14–19. Linear fit including all data points (red) and separated fits for the σ ≤ 0 (blue) and σ ≥ 0 (green) regions.

Without determination of the extinction coefficients of the different systems, the UV/vis analysis cannot be used for quantification of the SP/MC ratio. Since this can be challenging, the SP/MC ratios were determined via 1H NMR spectroscopy.

¹H NMR ratios of indole-substituted SPs and MCs

To gain insight into the relationship between indole substituents and SP/MC ratio, 1H NMR spectra of the systems 7, 14–19 were measured in methanol after exclusion of light as well as after exposure to visible light. For the determination of the isomeric ratio, the aromatic CH-signals were integrated and averaged. Only clearly separated signals were considered to ensure higher accuracy. Within a pair of isomers, the same signals were used for the integration. Since the chemical shift of the signals depends on the substituents, the same signals could not be used for all molecules.” Using the integral ratios, a correlation between the stability of the MC and substituents on the indole unit can be shown. Due to solubility problems in methanol, only the measurements of 7, 14, 17, and 18 could be used. Nevertheless, a clear trend can be observed. At thermal equilibrium in the dark, 53% of MC were determined for the unsubstituted compound 7. For 14 and 17 with additional EDG at the indole, the amount of MC was increased to 76% and 70%, respectively. For the nitro-substituted derivative 18 on the other hand, only traces of MC were detected in the dark. After irradiation with visible light, the SP form was detected almost exclusively for all compounds (<5% MC). All NMR spectra can be found in the SI (Spectrum 76–86).

The experiments were repeated using DMSO-d ₆ ([Table 3]). Overall, the solubility in DMSO-d ₆ was better and therefore the SP/MC ratios for all seven derivatives could be analyzed. At thermal equilibrium in the dark, the highest amount of MC is detected for the methoxy-substituted compound 14 (94%) followed by 17 (77%) with a methyl group. Compared to the nonsubstituted 7 (64%), the amount of detected MC is highly decreased for the derivatives with EWG. While for the weak withdrawing bromine substituent, a decrease of the MC to 32% is observed; for the compounds with stronger EWG substituents at the indole, the amount of MC is decreased to less than 10%. In case of the nitro-substituted molecule 18, only traces of the MC could be detected. For all derivatives, irradiation with visible light led to almost quantitative conversion to the SP.

Table 3 ¹H NMR ratios (DMSO-d ₆) of SP/MC for indole-substituted derivatives 7, 13–19 at thermal equilibrium and after irradiation with visible light

System	Substituent	%MC dark	%MC vis
14	OMe	94%	<5%
17	Me	77%	<5%
7	H	64%	<5%
16	Br	32%	<5%
15	COOH	8%	<5%
19	NMe3I	9%	<5%
18	NO2	<5%	<5%

Correlation between the Observed Trends and the Change in Dipole Moment Utilizing DFT Calculations

MCs are known for their zwitterionic character and hence their high dipole moment. Compound 14, for which the smallest rate constant and the highest amount of MC at thermal equilibrium were observed, exhibits a strong push–pull character. This leads to the assumption that the stability of the MC and thus also the rate constant may be related to its dipole moment. Therefore, the dipole moments of all synthesized SP/MC were calculated using DFT. To obtain a holistic dataset, additional SP/MC derivatives were also calculated (for all data see SI, Tables 2–5). The MC form exists in different isomers. For each MC, all four stable transoid isomers were calculated, and their dipole moments were then averaged. The nomenclature of the different isomers can be seen in in [Table 4] based on the TTC isomer (or, more detailed, in the SI, Scheme 44). Since a switchable system is considered, the dipole moment of the SP is subtracted from the one of the MC to be able to scrutinize the dipole moment changes upon switching.

Table 4 Dipole moments of selected derivatives, calculated using DFT. For the merocyanine, a dipole moment range is given, since four different isomers (TTC, CTC, TTT and CTT) were calculated

Substituents			Dipole moment μ in Debey [D]a			k obs d
R	R′	R″	SP	MCb	MC–SPc
H	H	H	1.38	5.91–7.36	5.21	1.3 × 10−1
NO2	NO2	H	6.44	16.19–16.52	9.91	1.5 × 10−5
Ome	OMe	H	2.64	4.64–7.37	2.79	n.d.
NO2	Br	H	5.30	13.07–13.64	8.02	2.7 × 10−5
NO2	Br	NO2	6.91	6.24–7.76	0.19	3.1 × 10−2
NO2	Br	OMe	6.60	15.15–16.14	8.99	1.7 × 10−5

^aCalculated using the functional B3LYP D3BJ with the def2-QZVPPD basis set.

^bRange of dipole moments calculated for the four isomers.

^cAverage over all four isomers.

^dRate constant calculated based on UV/vis spectroscopy.

To assess the results from the DFT calculation, the relation between the MC and the push–pull system needs to be understood. The stability of the MC can be altered by changing either the nucleophilicity of the phenolate or the electrophilicity of the indole moiety. At the phenolate moiety, EWG substituents like nitro groups lower the electron density at the oxygen via both mesomeric and inductive effects. Therefore, the nucleophilicity of the phenolate is reduced, which disfavors the cyclization toward the SP and hence stabilizes the MC. EDG substituents like methoxy groups on the other hand increase the nucleophilicity of the phenolate and promote cyclization to the SP.

The DFT calculations for the benzopyran-substituted derivatives indicate similar trends. Compared with the unsubstituted MC (Δμ = 5.21 D), for those functionalized with EWG, significantly higher differences in dipole moments were calculated, while EDG decreased the differences. For system 9 with two nitro groups at the benzopyran, a dipole moment difference of Δμ = 9.91 D is found. For the system with two methoxy substituents, the calculated difference is Δμ = 2.79 D. The combination of EDG and EDG at the benzopyran reduces the impact of both groups, which is true for the rate constants and the dipole moments. Deviating from the trend that ortho-substituents have lesser impact on the rate constant, this trend cannot be seen for the dipole moments. It is important to mention that the substituents in the ortho position do not only contribute via electronic but also via steric effects.

As already mentioned, altering the electrophilicity of the indole party of the SP/MC system has a huge impact on the stability of the MC. EWG substituents increase the electrophilicity of the indole, which therefore can better react with the phenolate during the cyclization toward the SP and hence disfavors the MC. EDG substituents on the other hand reduce the electrophilic character of the indole, which leads to a less stable SP and a stabilized MC. Again, the same trends can be observed regarding the difference in dipole moment. While for compound 7 with no substituent at the indole moiety, a difference of Δμ = 2.79 D was calculated, the nitro substituent of 18 decreases the difference to Δμ = 0.18 D, and the EDG methoxy substituent of 14 leads to an increase to Δμ = 8.99 D. This trend is again in line with the previously discussed rate constants and the SP/MC ratios. The only exception is represented by derivative 14 with the trimethyl ammonium substituent. In this case, a very high difference in dipole moment of Δμ = 13.14 D was calculated. This deviation from the otherwise clear trends is most likely due to the positive charge of the ammonium substituent and the resulting overall very high dipole moment (μ _SP = 24.25 D; μ _MC = 34.40–38.74 D).

Conclusion

Over the past few decades, SPs have been established as reliable and versatile switchable compounds. The high impact of substituents at the benzopyran moiety on the photochromic character is already known. However, in this work, these effects could be investigated further. A clear trend between EWG substituents and the stabilization of the MC as well as a decrease of the rate constant of the thermal SP/MC isomerization was shown. In addition, a reverse trend for the substituent influence at the indole unit was observed. Furthermore, a potential connection between these trends and the dipole moments of the SP and MC derivatives could be observed.

All chemicals were bought from Sigma Aldrich, TCI, Fisher Scientific, Carl Roth and BLD Pharm and were, if not mentioned otherwise, directly used without further purification. All solvents were purchased in technically grade and freshly distilled prior use. Dry solvents were purchased from Acros Organic/Thermo Fisher Scientific over molecular sieve under Acroseal™. HPLC and LCMS grade solvents were purchased from Fisher Scientific. As inert gas, BIP© Argon (O₂ < 10 ppb, H₂O < 20 ppb, CO + CO₂ < 100 ppb) from AirProducts was used. For TLC, aluminum plates coated with Silicagel by Merck (Silica 60, F₂₅₄) were used. Silica gel for column chromatography was purchased from Acros Organics (0.035−0.070 mm, 60 Å).

¹H NMR-spectra were recorded with Avance 300 (300 MHz), Avance 500 (500 MHz), and AVANCE II+ 600 spectrometers by Bruker. The chemical shifts are referenced to TMS (δ = 0 ppm) (¹H-spectra) or the characteristic solvent signals (¹³C-spectra). ¹³C NMR spectra were recorded with 75 MHz or 125 MHz. The assignment of the ¹H and ¹³C resonances was obtained from ¹H COSY, ¹H, ¹³C HSQC, and HMBC experiments. IR spectra were recorded using an IRAffinity-1S FT-IR spectrometer by Shimadzu at 25 °C. Absorption bands are given in wavenumbers (ν [cm^-1]) and marked as s (strong), m (medium), or w (weak) with a prefixed “br” indicating broad signals. High-resolution ESI-MS spectra were obtained using a Thermo Scientific LTQ Orbitrap XL spectrometer with an FTMS analyzer using a spray voltage of 3.2 KV. GC-MS analysis was performed using a Hewlett-Packard HP 6890 Series gas chromatograph coupled with a HP 5973 mass detector column: HP-5: Crosslinked Methyl silicone gum capillary column, 25 m, 0.2 μm, 0.33 μm. Carrier gas: H₂. Temperature program: 50 °C (2 min), 20 °C/min, 280 °C (10 min). UV/vis analysis was performed using a Jasco V-730 spectrometer with an ETCS-761 Peltier thermostatic single position cell holder. All measurements were performed in 0.025 mm solutions at 20 °C using HPLC or LCMS grade solvents. Suprasil® 110-QS cuvettes by the company Hellma were used.

The ORCA 5.0 software package[15] was used for all calculations. The calculations were performed on the CHEOPS HPC cluster of the University of Cologne IT Center. Geometry optimization of the structures was performed using the B3LYP hybrid functional with the D3BJ dispersions correction and the def2-TZVPPD triple-ζ basis set with polarization functions for light and heavy atoms and a set of diffuse functions.[16] Frequency analysis of the optimized structures was done to exclude negative frequencies. Afterward, the single-point energy of the optimized structure was calculated using the B3LYP D3BJ functional and the def2-QZVPPD quadruple-ζ basis set with polarization functions for light and heavy atoms and a set of diffuse functions.

Procedures

Spiropyran Synthesis from 1,2,3,3-Tetramethyl-3H-indol-1-ium Iodide: General Procedure 1

Under argon atmosphere, 1,2,3,3-tetramethyl-3H-indol-1-ium iodide (1.0 eq.) and the corresponding salicylic aldehyde derivative (1.0 eq.) were dissolved in dry ethanol and heated to reflux overnight (16 h). After cooling to ambient temperature, the precipitate was filtered off and dried under reduced pressure. The isolated MC HI salt was suspended in ethanol and triethylamine (1.1 eq.) and stirred for 15 min at ambient temperature. The solvent was removed under reduced pressure and the crude product was recrystallized from water.

Spiropyran Synthesis from Fisher Base: General Procedure 2

Under argon atmosphere, Fischer’s base (1.0–1.2 eq.) and the corresponding salicylic aldehyde (1.0 eq.) were dissolved in EtOH and heated to reflux overnight (16–18 h) or over the weekend (2.5–3 d). The product was isolated by column chromatography or via filtration and recrystallization.

Synthesis of Indole-substituted SPs: General Procedure 3

Under argon atmosphere, substituted indolium iodide 30–35 (1.0 eq.), salicylic aldehyde (1.1 eq.), and Et₃N (1.1 eq.) were suspended in dry EtOH and heated to reflux overnight. After cooling to ambient temperature, the precipitate was filtered off and dried under reduced pressure.

1′,3′,3′-Trimethylspiro[chromene-2,2′-indoline] (1)

Synthesized following general procedure 2 using 620 mg of Fischer’s base (3.60 mmol, 1.0 eq.). After purification via column chromatography over silica gel (cHex/EtOAc 20:1; R _f = 0.7), SP (1) (930 mg, 3.35 mmol, 93%) was isolated as a colorless solid (mp.: 91–93 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3044 (w), 2965 (w), 2930 (w), 2903 (w), 2864 (w), 1649 (w), 1605 (w), 1576 (w), 1483 (m), 1454 (w), 1443 (w), 1418 (w), 1396 (w), 1383 (w), 1360 (w), 1302 (w), 1250 (m), 1217 (w), 1186 (w), 1171 (w), 1155 (w), 1140 (w), 1111 (m), 1067 (w), 1022 (m), 988 (w), 957 (s), 916 (w), 870 (w), 847 (w), 816 (m), 777 (m), 756 (s), 741 (s), 721 (m), 683 (w), 662 (w), 629 (w).

¹H NMR: (500 MHz, CDCl₃) δ [ppm] = 7.17 (td, ³ J = 7.6 Hz, ⁴ J = 1.3 Hz, 1H7.10–7.04 (m, 2H), 7.03 (dd, ³ J = 7.5 Hz, ⁴ J = 1.7 Hz, 1H), 6.87–6.77 (m, 3H), 6.70 (dd, ³ J = 8.1 Hz, ⁴ J = 0.9 Hz, 1H), 6.52 (d, ³ J = 7.7 Hz, 1H), 5.66 (d, ³ J = 10.2 Hz, 1H), 2.73 (s, 3H), 1.30 (s, 3H), 1.16 (s, 3H).

¹³C NMR: (75 MHz, CDCl₃) δ [ppm] = 154.6, 148.4, 136.9, 129.8, 129.5, 127.7, 126.8, 121.6, 120.1, 119.5, 119.2, 118.9, 115.1, 106.9, 104.3, 51.8, 29.1, 26.0, 20.3.

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₉NO: 278.1539408; found: 278.15406; [M+Na]⁺; calcd for C₁₉H₁₉NO: 300.1358855; found: 300.13618.

6-Bromo-1′,3′,3′-trimethylspiro[chromene-2,2′-indoline] (2)

Synthesized following general procedure 2 using 1.06 ml of Fischer’s base (6.00 mmol, 1.2 eq.). After purification via column chromatography over silica gel (cHex/EtOAc 50:1; R _f = 0.35), SP (1) (1.59 g, 4.46 mmol, 90%) was isolated as a colorless solid (mp.: 90–93 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3049 (w), 2963 (w), 2924 (w), 2866 (w), 2808 (w), 1639 (w), 1607 (w), 1474 (s), 1464 (s), 1420 (w), 1356 (m), 1298 (m), 1256 (s), 1213 (w), 1177 (m), 1124 (m), 1115 (m), 1103 (m), 1065 (w), 1020 (m), 951 (s), 924 (m), 874 (s), 829 (s), 814 (s), 746 (s), 710 (s), 677 (s), 621 (w).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 7.42 (d, ⁴ J = 2.5 Hz, 1H), 7.23 (dd, ³ J = 8.6 Hz, ⁴ J = 2.5 Hz, 1H), 7.13–7.08 (m, 2H, H-4), 7.02 (d, ³ J = 10.2 Hz, 1H), 6.78 (t, ³ J = 7.3 Hz, 1H), 6.65 (d, ³ J = 8.6 Hz, 1H), 6.57 (d, ³ J = 7.7 Hz, 1H), 5.85 (d, ³ J = 10.2 Hz, 1H), 2.65 (s, 3H), 1.21 (s, 3H), 1.09 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 153.2, 147.7, 136.1, 132.0, 129.1, 128.3, 127.5, 121.5, 120.9, 120.7, 119.1, 116.6, 111.2, 106.8, 104.3, 51.5, 28.5, 25.6, 19.8.

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₈BrNO: 356.0644534; found: 356.06438.

8-Bromo-1′,3′,3′-trimethylspiro[chromene-2,2′-indoline] (3)

Synthesized following general procedure 2 using 1.05 ml of Fischer’s base (6.00 mmol, 1.2 eq.). After purification via column chromatography over silica gel (cHex/EtOAc 30:1; R _f = 0.53), SP (1) (1.66 g, 4.66 mmol, 93%) was isolated as a colorless solid (turns purple >125 °C, mp.: 139–140 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3057 (w), 2963 (w), 2924 (w), 2868 (w), 1651 (w), 1607 (w), 1487 (m), 1443 (s), 1362 (w), 1302 (m), 1260 (m), 1209 (w), 1130 (w), 1103 (m), 1065 (w), 1022 (m), 966 (s), 876 (s), 858 (m), 795 (m), 743 (s), 718 (s), 619 (w).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 7.37 (dd, ³ J = 7.9 Hz, ⁴ J = 1.6 Hz, 1H), 7.20 (dd, ³ J = 7.5 Hz, ⁴ J = 1.6 Hz, 1H), 7.13–7.08 (m, 2H, H-4), 7.03 (d, ³ J = 10.2 Hz, 1H), 6.83–6.76 (m, 2H, H-5), 6.59 (d, ³ J = 7.6 Hz, 1H), 5.83 (d, ³ J = 10.2 Hz, 1H), 2.65 (s, 3H), 1.23 (s, 3H), 1.10 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 150.0, 147.5, 136.1, 132.7, 128.9, 127.5, 126.3, 121.4 (2C), 120.5, 120.4, 119.1, 108.1, 106.8, 105.2, 51.5, 28.5, 25.6, 20.0.

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₈BrNO: 356.0644534; found: 356.06430; [M+Na]⁺; calcd for C₁₉H₁₈BrNO: 378.0463980; found: 378.04631.

6,8-Dibromo-1′,3′,3′-trimethylspiro[chromene-2,2′-indoline] (4)

Synthesized following general procedure 1 using 1.40 g salicylic aldehyde (5.00 mmol, 1.0 eq.) yielding 2.53 g (4.49 mmol, 90%) of the intermediate HI salt. 1.12 g of the salt (2.00 mmol, 1.0 eq.) was used for the second step. SP (4) (0.66 g, 1.5 mmol, 75%) was isolated as a beige solid (mp.: 117–119 °C, turns blue upon melting).

FT-IR (ATR): ν̃ [cm⁻¹] = 3057 (w), 2963 (w), 2864 (w), 1649 (w), 1607 (w), 1549 (w), 1485 (m), 1445 (s), 1420 (m), 1360 (m), 1302 (m), 1261 (s), 1209 (w), 1153 (m), 1101 (m), 964 (s), 887 (s), 856 (m), 824 (w), 743 (s), 708 (s).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 7.58 (d, ⁴ J = 2.3 Hz, 1H), 7.48 (d, ⁴ J = 2.3 Hz, 1H), 7.15–7.09 (m, 2H), 7.03 (d, ³ J = 10.3 Hz, 1H), 6.79 (td, ³ J = 7.4 Hz, ⁴ J = 1.0 Hz, 1H), 6.60 (d, ³ J = 7.6 Hz, 1H), 5.92 (d, ³ J =10.3 Hz, 1H), 2.65 (s, 3H), 1.22 (s, 3H), 1.10 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = (126 MHz, DMSO-d ₆) δ [ppm] = 149.6, 147.4, 135.9, 134.0, 128.6, 128.0, 127.5, 122.0, 121.8, 121.4, 119.3, 111.4, 109.2, 106.9, 105.7, 51.7, 28.5, 25.6, 19.9.

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₇Br₂NO: 433.9749659; found: 433.97533; [M+Na]⁺; calcd for C₁₉H₁₇Br₂NO: 455.9569106; found: 455.95697.

1′,3′,3′-Trimethyl-6-nitrospiro[chromene-2,2′-indoline] (5)

Synthesized following general procedure 2 using 3.40 mL of Fischer’s base (20.3 mmol, 1.0 eq.) and a reaction time of 24 h. After recrystallization from ethanol, SP (5) (5.46 g, 16.9 mmol, 83%) was isolated as a yellow solid (turns blue >169 °C, mp.: 176–179 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 2963 (w), 2866 (w), 2816 (w), 1655 (w), 1609 (w), 1574 (w), 1508 (m), 1487 (m), 1477 (m), 1443 (m), 1423 (w), 1364 (w), 1331 (s), 1298 (m), 1269 (s), 1223 (w), 1184 (m), 1123 (m), 1088 (s), 1069 (w), 1015 (m), 949 (s), 912 (s), 837 (m), 806 (s), 781 (m), 748 (s), 716 (m), 681 (m), 627 (w).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 8.23 (d, ⁴ J = 2.8 Hz, 1H), 8.00 (dd, ³ J = 9.0 Hz, ⁴ J = 2.8 Hz, 1H), 7.23 (d, ³ J = 10.4 Hz, 1H), 7.14 (m, 2H), 6.89 (d, ³ J = 9.0 Hz, 1H), 6.82 (td, ³ J = 7.5 Hz, ⁴ J = 1.0 Hz, 1H), 6.62 (br, d, ³ J = 7.5 Hz, 1H), 6.00 (d, ³ J = 10.4 Hz, 1H), 2.68 (s, 3H), 1.22 (s, 3H), 1.12 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 159.4, 147.4, 140.5, 135.8, 128.3, 127.7, 125.7, 122.8, 121.5, 121.4, 119.4, 118.9, 115.4, 107.0, 106.1, 51.9, 28.5, 25.7, 19.7.

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₈N₂O₃: 323.1390190; found: 323.13872; [M+Na]⁺; calcd for C₁₉H₁₈N₂O₃: 345.1209636; found: 345.12097.

1′,3′,3′-Trimethyl-8-nitrospiro[chromene-2,2′-indoline] (6)

Synthesized following general procedure 1 using 501 mg salicylic aldehyde (3.00 mmol, 1.0 eq.) yielding (1.22 g, 2.71 mmol 90%) of the HI salt as a red solid, which was directly used in the second step. SP (6) (785 mg, 2.44 mmol, 81%) was isolated as a colorless solid (turns blue >127 °C, mp.: 147–149 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 2963 (w), 2866 (w), 1653 (w), 1607 (w), 1522 (m), 1454 (m), 1362 (m), 1302 (m), 1265 (s), 1177 (w), 1103 (m), 1074 (m), 1022 (m), 991 (w), 912 (s), 804 (s), 737 (s), 623 (w).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 7.70 (dd, ³ J = 8.2 Hz, ⁴ J = 1.5 Hz, 1H), 7.54 (dd, ³ J = 7.5 Hz, ⁴ J = 1.5 Hz, 1H), 7.17 (d, ³ J = 10.4 Hz, 1H), 7.00 (dd, ³ J = 8.2 Hz, ³ J = 7.5 Hz, 1H) 7.14–7.10 (m, 2H), 6.80 (td, ³ J = 7.4 Hz, ⁴ J 1.0 Hz, 1H), 6.63–6.57 (m, 1H), 5.97 (d, ³ J = 10.4 Hz, 1H), 2.67 (s, 3H), 1.26 (s, 3H), 1.11 (s, 3H,).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 147.2, 147.0, 136.7, 135.8, 131.5, 128.6, 127.5, 124.7, 121.4, 121.3, 121.0, 119.8, 119.4, 107.0, 106.2, 51.8, 28.5, 25.8, 19.6.

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₈N₂O₃: 323.1390190; found: 323.13858; [M+Na]⁺; calcd for C₁₉H₁₈N₂O₃: 345.1209636; found: 345.12058.

8-Bromo-1′,3′,3′-trimethyl-6-nitrospiro[chromene-2,2′-indoline] (7)

Synthesized following general procedure 2 using 0.59 mL of Fischer’s base (3.3 mmol, 1.0 eq.). The reaction was heated to reflux over the weekend (3 d). SP (7) (1.2 g; 2.9 mmol, 88%) was isolated as a dark green solid (turns purple >240 °C, mp.: 253–254 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3087 (w), 3051 (w), 3018 (w), 2980 (w), 2937 (w), 1587 (m), 1519 (s), 1434 (m), 1398 (m), 1323 (s), 1233 (s), 1116 (s),1069 (m), 1019 (m), 970 (m), 850 (m), 754 (s), 721 (m).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 8.28–8.25 (m, 2H), 7.25 (d, ³ J = 10.4 Hz, 1H), 7.17–7.10 (m, 2H), 6.83 (td, ³ J = 7.4 Hz, ⁴ J = 1.0 Hz, 1H), 6.65 (dd, ³ J = 8.1 Hz, ³ J = 1.0 Hz, 1H), 6.06 (d, ³ J = 10.4 Hz, 1H), 2.68 (s, 3H), 1.23 (s, 3H), 1.13 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 155.5, 147.1, 140.6, 135.7, 128.1, 128.0, 127.7, 122.2, 122.0, 121.5, 119.9, 119.6, 108.4, 107.8, 107.1, 52.0, 28.5, 25.7, 19.7.

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₇BrN₂O₃: 401.0495315; found: 401.04996; [M+Na]⁺; calcd for C₁₉H₁₇BrN₂O₃: 423.0314762; found: 423.03187.

6-Bromo-1′,3′,3′-trimethyl-8-nitrospiro[chromene-2,2′-indoline] (8)

Synthesized following general procedure 1 using 1.23 g salicylic aldehyde (5.00 mmol, 1.0 eq.) yielding 2.16 g (4.08 mmol, 82%) of the intermediate HI salt. 1.06 g of the salt (2.00 mmol, 1.0 eq.) were used for the second step. SP (4) (0.76 g, 1.89 mmol, 95%) was isolated as a dark-blue solid (mp.: 126–129 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3057 (w), 2974 (w), 2953 (w), 2870 (w), 1605 (w), 1530 (s), 1487 (s), 1456 (s), 1423 (m), 1358 (s), 1308 (m), 1267 (s), 1219 (m), 1175 (s), 1159 (m), 1101 (s), 1022 (s), 993 (m), 910 (s), 897 (s), 878 (s), 827 (m), 816 (s), 741 (s), 723 (s), 698 (s), 646 (m).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 7.93 (d, ⁴ J = 2.5 Hz, 1H), 7.81 (d, ⁴ J = 2.5 Hz, 1H), 7.16 (d, ³ J = 10.5 Hz, 1H), 7.15–7.11 (m, 2H), 6.81 (td, ³ J = 7.4 Hz, ⁴ J 1.0 Hz, 1H), 6.62 (d, ³ J = 7.5 Hz, 1H), 6.07 (d, ³ J = 10.5 Hz, 1H), 2.67 (s, 3H), 1.25 (s, 3H), 1.11 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 147.0, 146.2, 137.3, 135.7, 133.6, 127.7, 127.6, 126.5, 123.3, 122.4, 121.4, 119.5, 110.1, 107.1, 106.8, 51.9, 28.4, 25.8, 19.5.

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₇BrN₂O₃: 401.0495315; found: 401.04956; [M+Na]⁺; calcd for C₁₉H₁₇BrN₂O₃: 423.0314762; found: 423.03156.

1′,3′,3′-Trimethyl-6,8-dinitrospiro[chromene-2,2′-indoline] (9)

Synthesized following general procedure 2 using 1.77 mL of Fischer’s base (10.0 mmol, 1.0 eq.). The reaction was heated to reflux over the weekend (2.5 d). SP (9) (2.44 g, 6.64 mmol 66%) was isolated as a dark green solid (turns dark red >175 °C, decomp. at 248–250 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3041 (w), 3023 (w), 2996 (w), 1623 (m), 1549 (w), 1522 (s), 1453 (m), 1438 (s), 1414 (m), 1281 (s), 1236 (s), 1164 (m), 1078 (s), 1024 (m), 978 (s), 927 (m), 855 (w), 777 (s), 743 (w).

Merocyanine:

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 8.90 (d, ⁴ J = 3.3 Hz, 1H), 8.57 (d, ⁴ J = 3.3 Hz, 1H), 8.53 (d, ³ J = 15.8 Hz, 1H), 8.40 (d, ³ J = 15.8 Hz, 1H), 7.87–7.79 (m, 2H), 7.59 (td, ³ J = 7.5 Hz, ⁴ J = 1.5 Hz, 1H), 7.55 (td, ³ J = 7.5 Hz, ⁴ J = 1.1 Hz, 1H), 3.98 (s, 3H), 1.77 (s, 6H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 182.5, 169.5, 151.8, 143.3, 141.9, 140.9, 134.6, 128.8, 128.5, 128.2, 126.3, 125.3, 122.7, 114.5, 110.9, 51.5, 33.7, 25.9 (2C).

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₇N₃O₅: 368.1240971; found: 368.12396; [M+Na]⁺; calcd for C₁₉H₁₇N₃O₅: 390.1060418; found: 390.10612.

8-Methoxy-1′,3′,3′-trimethyl-6-nitrospiro[chromene-2,2′-indoline] (10)

Synthesized following general procedure 2 using 0.89 g of Fischer’s base (5.00 mmol, 1.0 eq.). After recrystallization from ethanol, SP (10) (0.81 g, 2.3 mmol, 45%) was isolated as a dark purple solid (mp.: 157–158 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3098 (w), 3048 (w), 2957 (w), 2930 (w), 2824 (w), 1655 (w), 1609 (w), 1578 (w), 1512 (s), 1487 (m), 1464 (m), 1450 (m), 1391 (m), 1360 (m), 1331 (s), 1310 (m), 1269 (s), 1252 (s), 1192 (m), 1179 (m), 1113 (s), 1094 (s), 1069

(m), 1015 (m), 980 (s), 930 (m), 897 (s), 849 (m), 820 (m), 793 (m), 775 (s), 737 (s), 727 (s), 658 (m), 638 (w), 606 (m).

¹H NMR: (500 MHz, CDCl₃) δ [ppm] = 7.70 (d, ³ J = 2.6 Hz, 1H), 7.62 (d, ³ J = 2.6 Hz, 1H), 7.19 (td, ³ J = 7.7 Hz, ⁴ J = 1.3 Hz, 1H), 7.07 (dd, ³ J = 7.6, ⁴ J = 1.3 Hz, 1H), 6.88 (d, ³ J = 10.4 Hz, 2H), 6.86 (dd, ³ J = 7.6 Hz, ⁴ J = 0.8 Hz, 1H), 6.55 (d, ³ J = 7.7 Hz, 1H), 5.83 (d, ³ J = 10.3 Hz, 1H), 3.76 (s, 3H), 2.75 (s, 3H), 1.29 (s, 3H), 1.18 (s, 3H).

¹³C NMR: (126 MHz, CDCl₃) δ [ppm] = 149.7, 147.8, 147.4, 140.5, 136.3, 128.3, 127.8, 121.9, 121.7, 119.6, 118.6, 115.5, 108.1, 107.0, 106.5, 56.5, 52.4, 28.9, 26.1, 20.2.

GC–MS: t _R = 17.31 min; m/z (%) = 352.2 [M]⁺ (74), 337.2 (31), 159.1 (100), 144.1 (53), 116.9 (10), 91 (10).

6-Methoxy-1′,3′,3′-trimethyl-8-nitrospiro[chromene-2,2′-indoline] (11)

Synthesized following general procedure 2 using 1.75 g of Fischer’s base (10.0 mmol, 1.0 eq.) and DMF instead of ethanol. The reaction was heated for 4 h. SP (11) (1.39 g, 3.9 mmol, 38%) was isolated as a brown solid (mp.: 109–111 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 2959 (w), 2934 (w), 2909 (w), 2332 (w), 1659 (w), 1647 (w), 1605 (w), 1576 (w), 1497 (w), 1479 (m), 1456 (s), 1441 (m), 1422 (w), 1395 (w), 1383 (w), 1362 (w), 1323 (w), 1304 (m), 1263 (s), 1248 (s), 1223 (m), 1175 (m), 1159 (w), 1140 (w), 1121 (w), 1099 (s), 1076 (m), 1016 (s), 980 (s), 922 (s), 874 (w), 851 (w), 816 (w), 797 (m), 777 (m), 739 (s), 725 (s), 694 (m), 658 (w), 642 (w), 625 (w).

¹H NMR: (500 MHz, CDCl₃) δ [ppm] = 7.21 (d, ⁴ J = 3.1 Hz, 1H), 7.15 (td, ³ J = 7.6 Hz, 1.4 Hz, 1H), 7.05 (d, ³ J = 7.2 Hz, 1H), 6.89–6.84 (m, 2H), 6.84 (td, ³ J = 7.4 Hz, ⁴ J = 1.1 Hz, 1H),, 6.52 (d, ³ J = 7.8 Hz, 1H,), 5.89 (d, ³ J = 10.2 Hz, 1H) 3.79 (s, 3H), 2.72 (s, 3H), 1.34 (s, 3H), 1.18 (s, 3H).

¹³C NMR: (126 MHz, CDCl₃) δ [ppm] = 151.7, 147.6, 142.8, 136.6, 136.1, 128.3, 127.7, 122.6, 122.3, 121.4, 119.7, 118.5, 108.7, 107.0, 105.8, 56.1, 52.0, 28.9, 26.0, 20.1.

GC-MS: t _R = 17.15 min; m/z (%) = 352.2 [M]⁺ (78), 335.2 (95), 305.1 (55), 290.1 (19), 194.1 (14), 159.1 (100),158.1 (64), 144.1 (31).

6-Methoxy-1′,3′,3′-trimethyl-spiro[chromene-2,2′-indoline] (12)

Synthesized following general procedure 2 using 0.580 mL of Fischer’s base (3.25 mmol, 1.0 eq.). The reaction was heated for 5 h. After purification via column chromatography over silica gel (cHex/EtOAc 99:1; R _f = 0.47), SP (12) (970 mg, 3.16 mmol, 98%) was isolated as an orange solid (mp.: 81–84 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 2959 (w), 2926 (w), 2905 (w), 2866 (w), 1607 (m), 1580 (w), 1483 (s), 1464 (s), 1454 (s), 1435 (m), 1420 (w), 1379 (w), 1360 (m), 1300 (m), 1248 (s), 1227 (m), 1179 (s), 1155 (m), 1140 (w), 1101 (m), 1067 (w), 1038 (s), 1015 (s), 962 (s), 924 (s), 868 (m), 841 (m), 812 (s), 791 (m), 739 (s), 729 (s), 710 (s), 646(w), 635 (w).

¹H NMR: (500 MHz, CDCl₃) δ [ppm] = 7.17 (td, ³ J = 7.6 Hz, ⁴ J = 1.3 Hz, 1H), 7.06 (dd, ³ J = 7.2 Hz, ⁴ J = 1.4 Hz, 1H), 6.87–6.76 (m, 2H), 6.70–6.62 (m, 2H), 6.60 (d, ⁴ J = 2.7 Hz, 1H), 6.51 (d, ³ J = 7.3 Hz, 1H), 5.70 (d, ³ J = 10.2 Hz, 1H, 3.75 (s, 3H), 2.72 (s, 3H), 1.30 (s, 3H), 1.16 (s, 3H).

¹³C NMR: (126 MHz, CDCl₃) δ [ppm] = 153.1, 148.3, 136.9, 129.3, 127.6, 121.5, 120.3, 119.1, 119.0, 115.5, 115.3, 111.5, 106.8, 103.9, 55.8, 51.6, 29.0, 25.9, 20.3.

GC-MS: t _R = 15.63 min; m/z (%) = 307.1 [M]⁺ (65), 292.1 (32), 277.2 (10), 159.1 (100), 144.1 (18), 77.1 (10).

8-Methoxy-1′,3′,3′-trimethyl-spiro[chromene-2,2′-indoline] (13)

Synthesized following general procedure 2 using 1.79 ml of Fischer’s base (10.0 mmol, 1.0 eq.) and 1.1 eq. of salicylic aldehyde. The reaction was heated for 3.5 h. SP (13) (2.11 g, 6.9 mmol, 69%) was isolated as a pale rose solid (mp.: 123–124 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 1605 (w), 1479 (m), 1456 (s), 1441 (m), 1422 (w), 1395 (w), 1362 (w), 1304 (m), 1263 (s), 1248 (s), 1223 (m), 1175 (m), 1159 (w), 1121 (w), 1099 (s), 1076 (m), 1016 (s), 980 (s), 922 (s), 816 (w), 797 (m), 777 (m), 739 (s), 725 (s), 694 (m), 658 (w).

¹H NMR: (500 MHz, CDCl₃) δ [ppm] = 7.15 (td, ³ J = 7.6, ⁴ J = 1.4 Hz, 1H), 7.05 (dd, ³ J = 7.2 Hz, ⁴ J = 1.4 Hz, 1H), 6.84–6.78 (m, 2H), 6.77–6.73 (m, 2H), 6.71–6.67 (m, 1H), 6.50 (d, ³ J = 7.7 Hz, 1H), 5.67 (d, ³ J = 10.2 Hz, 1H), 3.67 (s, 3H), 2.75 (s, 3H), 1.31 (s, 3H), 1.17 (s, 3H).

¹³C NMR: (126 MHz, CDCl₃) δ [ppm] = 148.2, 147.1, 144.0, 136.8, 129.2, 127.4, 121.5, 119.9, 119.7, 119.6, 119.3, 118.8, 114.2, 106.6, 104.3, 56.7, 51.6, 28.9, 25.8, 20.4.

GC-MS: t _R = 15.06 min; m/z (%) = 307.2 [M]⁺ (77), 292.1 (34), 264.2 (10), 220.1 (10), 159.1 (100), 144.1 (24), 77.1 (14).

8-Bromo-5′-methoxy-1′,3′,3′-trimethyl-6-nitrospiro[chromene-2,2′-indoline] (14)

Synthesized following general procedure 3 using indolium iodide (30) (3.31 g, 10.0 mmol, 1.0 eq.), After washing the filtered solid, SP (14) (4.28 g, 9.92 mmol, 99%) was isolated as a black solid (239–241 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3078 (w), 3054 (w), 2997 (w), 2981 (w), 2970 (w), 2900 (w), 2836 (w), 1607 (m), 1586 (m), 1532 (s), 1431 (m), 1397 (w), 1297 (s), 1277 (s), 1238 (s), 1219 (s), 1137 (m), 1045 (w), 1018 (m), 846 (m), 742 (m).

Spiropyran

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 8.26 (d, ⁴ J = 2.7 Hz, 1H), 8.25 (d, ⁴ J = 2.8 Hz, 1H), 7.24 (d, ³ J = 10.4 Hz, 1H), 6.81 (d, ⁴ J = 2.6 Hz, 1H), 6.70 (dd, ³ J = 8.4 Hz, ⁴ J = 2.6 Hz, 1H), 6.56 (d, ³ J = 8.4 Hz, 1H), 6.04 (d, ³ J = 10.3 Hz, 1H), 3.71 (s, 3H), 2.61 (s, 3H), 1.22 (s, 3H), 1.14 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 155.7, 153.8, 141.2, 140.5, 137.3, 128.1, 128.0, 122.1, 122.0, 119.9, 111.5, 109.2, 108.5, 108.4, 107.4, 55.4, 52.1, 28.8, 25.5, 19.6

Merocyanine

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 8.70 (d, ⁴ J = 3.0 Hz, 1H), 8.42 (d, ³ J = 15.6 Hz, 1H, H-12), 8.32 (d, ³ J = 15.6 Hz, 1H), 8.24 (d, ⁴ J = 3.0 Hz, 1H), 7.69 (d, ³ J = 8.8 Hz, 1H), 7.46 (d, ⁴ J = 2.5 Hz, 1H), 7.10 (dd, ³ J = 8.8 Hz, ⁴ J = 2.5 Hz, 1H), 3.91 (s, 3H), 3.87 (s, 3H), 1.75 (s, 6H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 180.2, 173.3, 159.9, 152.1, 145.0, 135.3, 132.2, 130.6, 129.4, 120.5, 119.5, 115.0, 114.2, 109.0, 108.7, 56.0, 51.1, 33.3, 26.2 (2C).

HRMS (ESI): m/z [M+H]⁺; calcd for C₂₀H₁₉BrN₂O₄: 431.0600962; found: 431.06046; [M+Na]⁺; calcd for C₂₀H₁₉BrN₂O₄: 453.0420409; found: 453.04249.

8-Bromo-1′,3′,3′-trimethyl-6-nitrospiro[chromene-2,2′-indoline]-5′-carboxylic acid (15)

Synthesized following general procedure 3 using indolium iodide (31) (0.50 g, 1.5 mmol, 1.0 eq.). SP (15) (0.57 g, 1.3 mmol, 89%) was isolated as a yellow solid (turns dark >235 °C, mp.: 268–271 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3092 (w), 2965 (w), 2874 (w), 2816 (br, w), 2639 (br, w), 1668 (m), 1609 (m), 1512 (s), 1439 (m), 1366 (m), 1333 (s), 1290 (s), 1258 (s), 1090 (s), 1055 (m), 1024 (m), 968 (s), 918 (s), 860 (s), 758 (s), 743 (s), 721 (s).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 12.44 (s, br, 1H), 8.28 (s, 2H), 7.83 (dd, ³ J = 8.2, ⁴ J = 1.8 Hz, 1H), 7.70 (d, ⁴ J = 1.8 Hz, 1H), 7.29 (d, ³ J = 10.4 Hz, 1H), 6.74 (d, ³ J = 8.2 Hz, 1H), 6.10 (d, ³ J = 10.4 Hz, 1H), 2.77 (s, 3H), 1.26 (s, 3H), 1.15 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 167.4, 155.2, 151.0, 140.8, 135.8, 130.9, 128.4, 128.1, 122.9, 122.1, 121.8, 121.7, 119.8, 108.4, 107.5, 106.4, 51.7, 28.4, 25.4, 19.6.

HRMS (ESI): m/z [M+H]⁺; calcd for C₂₀H₁₇BrN₂O₅: 445.0393607; found: 445.03983.

5′,8-Dibromo-1′,3′,3′-trimethyl-6-nitrospiro[chromene-2,2′-indoline] (16)

Synthesized following general procedure 3 using indolium iodide (32) (1.14 g, 3.00 mmol, 1.0 eq.). SP (16) (1.3 g, 2.7 mmol 79%) was isolated as a dark-grey solid (turns dark >235 °C, mp.: 249–250 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3102 (w), 2983 (w), 2936 (w), 1598 (m), 1511 (s), 1441 (m), 1399 (m), 1291 (s), 1204 (s), 1167 (m), 1120 (m), 1081 (s), 960 (m), 823 (m), 745 (w), 730 (m).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 8.28 (d, ⁴ J = 2.7 Hz, 1H), 8.27 (d, ⁴ J = 2.7 Hz, 1H), 7.35 (d, ⁴ J = 2.1 Hz, 1H), 7.30 (dd, ³ J = 8.3, ⁴ J = 2.1 Hz, 1H), 7.27 (d, ³ J = 10.4 Hz, 1H), 6.64 (d, ³ J = 8.3 Hz, 1H), 6.06 (d, ³ J = 10.4 Hz, 1H), 2.67 (s, 3H), 1.23 (s, 3H), 1.14 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 155.3, 146.5, 140.7, 138.5, 130.2, 128.4, 128.1, 124.7, 122.1, 121.7, 119.8, 110.7, 109.1, 108.4, 107.6, 52.1, 28.5, 25.2, 19.4.

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₆Br₂N₂O₃: 433.9749659; found: 433.97533; [M+Na]⁺; calcd for C₁₉H₁₆Br₂N₂O₃: 500.9419888; found: 500.94274.

8-Bromo-1′,3′,3′,5′-tetramethyl-6-nitrospiro[chromene-2,2′-indoline] (17)

Synthesized following general procedure 3 using indolium iodide (33) (600 mg, 2.00 mmol, 1.0 eq.). SP (17) (820 mg, 1.96 mmol, 98%) was isolated as a green solid (turns dark purple >230 °C, mp.: 245–248 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3087 (w), 3055 (w), 2984 (w), 2973 (w), 2932 (w), 1586 (m), 1519 (s), 1432 (m), 1397 (m), 1355 (w), 1301 (m), 1276 (s), 1232 (s), 1167 (m), 1136 (w), 1119 (s), 1070 (m), 970 (m), 847 (m), 742 (m), 696 (m).

Spiropyran

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 8.28–8.21 (m, 2H), 7.24 (d, ³ J = 10.4 Hz, 1H), 6.97 (s, 1H), 6.95–6.93 (m, 1H), 6.54 (d, ³ J = 7.8 Hz, 1H), 6.05 (d, ³ J = 10.3 Hz, 1H), 2.64 (s, 3H), 2.26 (s, 3H), 1.22 (s, 3H), 1.12 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 155.6, 145.0, 140.5, 135.8, 128.2, 128.1, 128.0, 127.8, 122.3, 122.2, 122.0, 119.9, 108.4, 108.1, 106.9, 52.0, 28.6, 25.7, 20.7, 19.8.

Merocyanine

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 8.72 (d, ⁴ J = 3.1 Hz, 1H), 8.44 (d, ³ J = 15.5 Hz, 1H), 8.37 (d, ³ J = 15.5 Hz, 1H), 8.32–8.20 (m, 1H), 7.65 (d, ³ J = 8.3 Hz, 1H), 7.61 (d, ⁴ J = 1.6 Hz, 1H), 7.37 (dd, ³ J = 8.3 Hz, ⁴ J = 1.6 Hz, 1H), 3.90 (s, 3H), 2.44 (s, 3H), 1.74 (s, 6H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 181.2, 173.4, 153.2, 143.1, 139.9, 138.0, 132.6, 130.8, 129.5, 129.1, 123.2, 120.5, 119.6, 113.6, 108.8, 50.9, 33.2, 26.2 (2C), 21.1.

HRMS (ESI): m/z [M+H]⁺; calcd for C₂₀H₁₉BrN₂O₃: 415.0651816; found: 415.06537; [M+Na]⁺; calcd for C₂₀H₁₉BrN₂O₃: 437.0471263; found: 437.04736.

8-Bromo-1′,3′,3′-trimethyl-5′,6-dinitrospiro[chromene-2,2′-indoline] (18)

Synthesized following general procedure 3 using indolium iodide (34) (600 mg, 2.00 mmol, 1.0 eq.). SP (18) (820 mg, 1.96 mmol, 98%) was isolated as a green solid (turns dark >190 °C, melts at 222–224 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3078 (w), 2968 (w), 2938 (w), 1603 (m), 1516 (s), 1491 (s), 1441 (m), 1312 (s), 1287 (s), 1269 (s), 1260 (s), 1225 (m), 1206 (w), 1177 (m), 1123 (m), 1107 (s), 1090 (s), 1051 (m), 1020 (s), 968 (s), 930 (s), 905 (s), 868 (s), 843 (m), 814 (s), 772 (m), 760 (m), 719 (s).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 8.31 (s, 2H), 8.17 (dd, ³ J = 8.7 Hz, ⁴ J = 2.4 Hz, 1H), 8.08 (d, ⁴ J = 2.4 Hz, 1H), 7.32 (d, ³ J = 10.4 Hz, 1H), 6.87 (d, ³ J = 8.7 Hz, 1H), 6.12 (d, ³ J = 10.4 Hz, 1H), 2.85 (s, 3H), 1.31 (s, 3H), 1.19 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 154.7, 152.7, 141.1, 140.1, 136.8, 128.6, 128.2, 126.2, 122.2, 121.1, 119.7, 118.1, 108.5, 107.2, 106.3, 51.7, 28.5, 25.0, 19.3.

HRMS (ESI): m/z [M+H]⁺; calcd for C₁₉H₁₆BrN₃O₅: 446.0346097; found: 446.03503; [M+Na]⁺; calcd for C₁₉H₁₆BrN₃O₅: 468.0165544; found: 468.01708.

8-Bromo-N,N,N,1′,3′,3′-hexamethyl-6-nitrospiro[chromene-2,2′-indolin]-5′-aminium Iodide (19)

Synthesized following general procedure 3 using indolium iodide (35) (500 mg, 1.40 mmol, 1.0 eq.). SP (19) (609 mg, 1.04 mmol, 71%) was isolated as a pale red solid (turns dark >160 °C, mp.: 196–198 °C).

FT-IR (ATR): ν̃ [cm⁻¹] = 3080 (w), 3007 (w), 2963 (w), 1655 (w), 1614 (w), 1589 (w), 1520 (s), 1497 (m), 1449 (w), 1437 (w), 1375 (w), 1341 (s), 1312 (m), 1275 (m), 1206 (w), 1092 (m), 1022 (w), 972 (m), 951 (w), 924 (w), 862 (s), 806 (w), 743 (m), 721 (m), 696 (w), 679 (w).

¹H NMR: (500 MHz, DMSO-d ₆) δ [ppm] = 8.30 (s, 2H), 7.83 (d, ⁴ J = 2.8 Hz, 1H), 7.70 (dd, ³ J = 8.7 Hz, ⁴ J = 2.8 Hz, 1H), 7.29 (d, ³ J = 10.3 Hz, 1H), 6.81 (d, ³ J = 8.8 Hz, 1H), 6.08 (d, ³ J = 10.3 Hz, 1H), 3.58 (s, 9H), 2.75 (s, 3H), 1.30 (s, 3H), 1.17 (s, 3H).

¹³C NMR: (126 MHz, DMSO-d ₆) δ [ppm] = 155.5, 148.2, 141.4, 140.7, 137.8, 128.8, 128.6, 122.6, 122.1, 120.6, 120.3, 114.9, 108.8, 107.8, 107.0, 57.2 (3C), 52.7, 28.9, 26.0, 20.1.

HRMS (ESI): m/z [M−I]⁺; calcd for C₂₂H₂₅BrIN₃O₃: 458.1073808; found: 458.10800.

Niklas Hermes

Niklas Hermes studied organic chemistry at the University of Cologne, Germany, focusing on synthesis and catalysis. In 2019, he joined the group of Ralf Giernoth for his PhD studies on the synthesis and characterization of spiropyran-based photoswitchable molecules and small proline-centered peptides. His research has a special emphasis on the photophysical properties and dipole moments of the photochromic systems.

Ralf Giernoth

Ralf Giernoth studied chemistry at the University of Bonn, Germany. After doing postdoctoral research at the University of Oxford/UK, he went to the University of Cologne, Germany, where he became Professor for Organic Chemistry. His research interests include interactions in solution, switchable molecules, photochemistry, and experimental NMR spectroscopy.

Contributors’ Statement

Niklas Hermes: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing – original draft. Sirin Vogt: Investigation. Vanessa Gruber: Investigation. Rebecca F Maier: Investigation. Kimia Niazkar: Investigation. Ralf Wolfgang Giernoth: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Writing – review & editing.

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgement

We thank the Regional Computing Center of the University of Cologne (RRZK) for providing computing time on the DFG-funded (Funding number: INST 216/512/1FUGG) High Performance Computing (HPC) system CHEOPS as well as support.

• References

• 1a Jerca FA, Jerca VV, Hoogenboom R. Nat Rev Chem 2022; 6: 51-69
• 1b Beharry AA, Woolley GA. Chem Soc Rev 2011; 40: 4422-4437
• 2a Irie M. Chem Rev 2000; 100: 1685-1716
• 2b Tian H, Yang S. Chem Soc Rev 2004; 33: 85-97
• 2c Bag SK, Pal A, Jana S, Thakur A. Chem Asian J 2024; 19: e202400238
• 3a Lerch MM, Szymański W, Feringa BL. Chem Soc Rev 2018; 47: 1910-1937
• 3b Duan Y, Shao H, Xiong C, Mao L, Wang D, Sheng Y. Chin J Chem 2021; 39: 985-998
• 4a Kortekaas L, Browne R. Chem Soc Rev 2019; 48: 3406-3424
• 4b Paramonov SV, Lokshin V, Fedorova OA. J Photochem Photobiol, C 2011; 12: 209-236
• 5a Goulet-Hanssen A, Eisenreich F, Hecht S. Adv Mater 2020; 32: 1905966
• 5b Klajn R. Chem Soc Rev 2014; 43: 148-184
• 5c Rad JK, Balzade Z, Mahdavian AR. J Photochem Photobiol, C 2022; 51: 100487
• 6a Peddie V, Abell AD. J Photochem Photobiol, C 2019; 40: 1-20
• 6b Li H, Vaughan JC. Chem Rev 2018; 18: 9412-9454
• 6c Lukinavičius G, Johnsson K. Curr Opin Chem Biol 2011; 12: 768-774
• 6d Ali AA, Kharbash R, Kim Y. Anal Chim Acta 2020; 1110: 199-223
• 7a Hirshberg Y. C R Acad Sci 1950; 231: 903-904
• 7b Hirshberg YM, Fischer E. J Chem Soc 1954; 297-303
• 8a Chen S, Jiang F, Cao Z, Wang G, Dang Z-M. Chem Commun 2015; 51: 12633-12636
• 8b Wan S, Zheng Y, Shen J, Yang W, Yin M. Appl Mater Interfaces 2014; 6: 19515-19519
• 8c Wojtyk JTC, Wasey A, Xiao N-N. et al. J Phys Chem A 2007; 111: 2511-2516
• 9a Piard J. J Chem Educ 2014; 91: 2105-2211
• 9b Tian W, Tian J. Dyes Pigments 2014; 105: 66-74
• 10a Qui W, Gurr PA, da Silva G, Qiao GG. Polym Chem 2019; 10: 1650-1659
• 10b Zhang H, Chen Y, Lin Y. et al. Macromolecules 2014; 47: 6783-6790
• 11a Wimberger L, Prasad SKK, Peeks MD, Andréasson J, Schmidt TW, Beves JE. J Am Chem Soc 2021; 143: 20758-20768
• 11b Brügner O, Reichenbach T, Sommer M, Walter M. J Phys Chem A 2017; 121: 2683-2687
• 12a Berman E, Fox RE, Thomson FD. J Am Chem Soc 1959; 21: 5605-5608
• 12b Liu J, Tang W, Sheng L. et al. Chem Asian J 2019; 14: 438-445
• 12c Balmond EI, Tautges BK, Faulkner AL. et al. J Org Chem 2016; 81: 8744-8758
• 13 Roxburgh CJ, Sammes PG, Abdullah A. Dyes Pigments 2009; 82: 226-237
• 14 Shiraishi Y, Yomo K, Hirai T. ACS Phys Chem Au 2023; 3: 290-298
• 15 Neese F. Wiley Interdiscip Rev Comput Mol Sci 2012; 1: 73-78
• 16a Weigend F. Phys Chem Chem Phys 2006; 8: 1057-1065
• 16b Weigend F, Ahlrichs R. Phys Chem Chem Phys 2005; 7: 3297-3305
• 16c Rappoport D, Furche F. J Chem Phys 2010; 133: 134105
• 16d Becke AD. J Chem Phys 1993; 98: 1372-1377
• 16e Stephens PJ, Devlin FJ, Chabalowski CF, Frisch MJ. J Phys Chem 1994; 98: 11623-11627
• 16f Grimme S, Antony J, Ehrlich S, Krieg H. J Chem Phys 2010; 132: 154104
• 16g Grimme S, Ehrlich S, Goerigk L. J Comput Chem 2011; 32: 1456-1465

Publication History

Received: 21 July 2025

Accepted after revision: 14 September 2025

Article published online:
29 September 2025