RU2358977C1 - 5-formyl-substituted indoline spirobenzopyrans and method of producing them - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds, and more specifically to 5-formyl-substituted indoline spirobenzopyrans with general formula 1

where R₁, R₂ - Alk or c-Alk; R₃ -CHO or NO₂ group (electron-acceptor substitute), with photochromic properties. The invention also relates to the method of producing 5-formyl substituted derivatives of indoline spirobenzopyrans with formula 1. Spirobenzopyrans, which have electron-acceptor substitutes in the pyran part of the molecule, are subjected to direct selective formylation in position 5 in a trifluoroacetic acid medium with urotropine (hexamethylenetetramine) at boiling point of the mixture in an inert atmosphere for 1-1.5 hours. The obtained 5-formyl-substituted spirobenzopyrans are photochromic compounds are photochromic and can be used for making new photochromic materials (recording devices or information storage; photo-switching activity of biological objects and polymer matrices, complex formation; information security media, maps, special document protection equipment) or as advanced initial compounds for further synthesis of a large number of new photochromic objects.

EFFECT: wider field of application of the compounds.

2 cl, 1 tbl, 3 ex

Description

The present invention relates to a convenient method of functional modification of classical photochromic indoline spiropyranes (SP) according to the indoline fragment of the molecule, to obtain new 5-formyl-substituted spirobenzopyranes of the general formula SP-5-CHO

Formylation reaction of indoline spirobenzopyranes

where R ₁ , R ₂ - Alk or c-Alk,

R ₃ - CHO or NO ₂ group (electron-acceptor substituent).

Photochromic compounds include substances that are capable of reversible conversion from one state to another, occurring in at least one direction under the influence of light and accompanied by a change in absorption in the visible region of the spectrum. To date, the main areas of application of photochromic compounds and materials are: information storage devices and recording devices; photo-switching of the activity of biological objects and polymer matrices, complexation; information protection tools, ID-cards, special. document protection means; cosmetics, photo staining of clothing and art.

Indoline spirobenzopyranes are a well-known class of photochromic compounds. The most pronounced photochromic properties are possessed by spiropyran molecules with acceptor substituents in the pyran part, which increase the lifetime of the colored merocyanine form [Zakhs ER, Martynova VP, Efros LS Synthesis and properties of spiropyrans capable of reversible opening of the pyran ring. / CHC. 1979. No. 2. S.435-459]. Substitution of the indoline part of the molecule does not lead to significant changes in the absorption maximum of the colored form, the conditions and parameters of the photochromic reaction, it is often predictable, which makes the modification of the indoline fragment to be introduced into the required systems, media, or attached to the substrate [Pantsyrny V.I. Halberstam M.A., Donskaya N.A. On the effect of substituents at positions 5 and 8 'on the rate of dark bleaching reaction of photo-colored solutions of 1,3,3-trimethylspiro- [indoline-2,2 ′ - [2Н-1] benzopyranes]. HCG. 1973. No. 5. S.653-658. Pantsyrny V.I., Halberstam M.A. On the effect of substituents at positions 5 and 8 ′ on the absorption spectra of merocyanine forms of spiropyrans. HCG. 1973. No. 5. S.659-662].

The presence of the formyl group in the indoline part allows a large number of reactions to be carried out with its participation while maintaining the rest of the spiropyran molecule, for example, to attach linkers / spacers of various nature.

The classical method for the preparation of spiropyrans consists in the condensation of indolenin derivatives (1,3,3-trimethyl-2-methyleneindoline, Fischer base) or their quaternary salts with substituted salicylic aldehydes. The process is carried out by heating, while boiling in an inert atmosphere, solutions of the starting reagents in various solvents (alcohols, toluene, dimethylformamide) [Ono H., Osada C. Photochromic compound. / Patent 3692800 (US). 1972]. The product is isolated by crystallization or chromatography on a small layer of sorbent. However, such direct synthesis is often too expensive, complicated, or even impossible for a number of substituted spiropyranes due to problems with the availability and / or cost of the starting materials. Derivatives of salicylic aldehyde, as a rule, are available, quite stable during storage, are easily cleaned, their preparation is carried out by modification of salicylic aldehyde itself or formylation of phenol derivatives. Therefore, the optimal approach to obtain the desired substituent of the pyran fragment is the synthesis of spiropyrans from derivatives of salicylic aldehyde containing this substituent or a precursor group that is easily converted to the target. In contrast to salicylic aldehydes, the preparation of a number of indolenin derivatives is extremely difficult; the simplest and most accessible derivative is 1,3,3-trimethyl-2-methyleneindoline.

A number of electrophilic substitution reactions of derivatives of spiropyranes occurring at the 5th position of the indoline fragment are known in the literature [Zakhs E.R., Zvenigorodskaya L.A., Leshenyuk N.G., Martynova V.P. Bromination of spiropyrans and reduction of their nitro derivatives. / CHC. 1977. No. 10. S.1320-1326; Samoilova N.P., Halberstam M.A. About some substitution reactions in a series of photochromic indoline spirochromes. / CHC. 1977. No. 8. S.1065-1068; Halberstam M.A., Bondarenko E.M., Khrolova O.R. et al. Synthesis and photochromic properties of 5-acetyl-substituted indoline spirochromes].

However, it was also shown that during Vilsmeier formylation or acylation with systems: acetic anhydride in the presence of boron trifluoride etherate in chloroform; benzoyl chloride with aluminum trichloride in carbon disulfide or benzoyl chloride in dimethylaniline medium, the formyl or acyl group is introduced into position 3 ′ [Halberstam MA, Artamonova NN, Samoilova NP Synthesis of 3′-acyl-substituted indoline spiropyrans. / CHC. 1975. No2. S.197-203].

The technical result of the invention is to obtain 5-formyl-substituted indoline spirobenzopyranes, which can be used as the most promising starting compounds for the further synthesis of a large number of new photochromic objects.

The technical result of the invention is the method of regioselective administration of the formyl group at the 5th position of the indoline nucleus of the spiropyran molecule. We found that under the conditions of the Duff reaction, the direct formulation of photochromic spiropyranes having electron-acceptor substituents in the pyran part of the molecule mainly proceeds at the 5th position of the indoline core of the molecule. The optimal process conditions are heating in trifluoroacetic acid while boiling a mixture of the starting spiropyran and an excess of 2-4 equiv. urotropine (hexamethylenetetramine, BDC) in an inert atmosphere. Heating the reaction mass at temperatures below the boiling point leads to an increase in the reaction time, the need to increase the excess of urotropine and generally does not affect the overall yield of the reaction. Trifluoroacetic acid is a commercially available reagent, it is easily removed by distillation in vacuo, it mixes well with water, making the isolation of the reaction product simple, and the process is relatively cheap. Polyphosphoric and methanesulfonic acids are also used as a medium to increase the temperature of such reactions, however, for this class of compounds, the use of these reagents is not necessary. The presence of traces of oxygen noticeably reduces the yield of the reaction, increases the content of by-products, causes gumming and oxidation of the reaction mass, so it is necessary to carry out the formylation reaction in an inert atmosphere. The magnitude of the excess of urotropine depends on the structural features of the starting spiropyran, an insufficient amount of formulating agent can lead to a low degree of conversion of the starting spiropyran, large excesses of it can lead to an increase in the share of by-products, secondary substitution at positions 3 ′ and 7 can occur with large excesses of urotropine.

These spirobenzopyranes SP-5-CHO are photochromic compounds and can be used to further obtain new photochromic materials.

To illustrate the present invention, the following examples of experimental procedures for the formation of spiro pyranes are formulated.

Example 1. Method for the synthesis of 6′-nitro-1,3,3-trimethyl-5-formylindolin-2-spiro-2′-2H-chromene (I). To a solution of 5.0 g (15.5 mmol) of 1,3,3-trimethyl-6'-nitrospiro (indolin-2,2 '- [2H] chromene) in 30 ml of trifluoroacetic acid was added 8.7 g (62.0 mmol) of hexamethylenetetramine and heated at boiling for 1 hour in an argon atmosphere. Then the reaction mass was poured onto 200 ml of ice. The precipitate was filtered off. Flash chromatography on silica gel was used to isolate the target product; eluent — petroleum ether (bp 40–70 ° С) — methylene chloride (1: 3, v / v). Additionally, the product was purified by crystallization from alcohol. Received 4.6 g (13.1 mmol) of product (I) (85%), so pl. 168-170 ° C. R _f 0.35 ("Silufol" UV-254, Kavalier, Czech Republic, spot detection - exposure to the developed plate of natural light). Mass spectrum, m / z: 351, [M] ⁺ . ¹ H NMR Spectrum (DMSO-d ₆ , δ, ppm, J / Hz): 1.15 (3H, s.3a-CH ₃ ), 1.27 (3H, s, 3b-CH ₃ ), 2.82 (3H, s, 1-CH ₃ ), 6.04 (1H, d, J 10.4, 3′-H), 6.81 (1H, d, J 8.3, 7-H), 6.93 (1H, d, J 9.0. 8′-H ), 7.28 (1H, d, J 10.3, 4′-H), 7.65 (1H, d, J 1.5, 4-H), 7.76 (1H, dts, J 8.1 / 1.5, 6-H), 8.02 (1H dd, J 9.0 / 2.9, 7′-H), 8.25 (1H, d, J 2.9, 5′-H), 9.77 (1H, s, 5-CHO).

Found (%): C, 67.98; H, 5.33; N, 8.02; O, 18.67. C ₂₀ H ₁₈ N ₂ O ₄ . Calculated (%): C, 68.56; H, 5.18; N, 8.0; Oh, 18.27. The spectral-kinetic characteristics (I) are shown in Table 1.

Example 2. 8′-Nitro-1,3,3-trimethyl-5-formylindoline-2-spiro-2′-2H-chromene (II). Compound (II) was obtained, isolated and purified analogously to (I) (Example 1) from 5 g (15.5 mmol) and 1,2,3-trimethyl-8'-nitrospiro (indolino-2,2 '- [2H] chromene) and 8.7 g (62.0 mmol) of hexamethylenetetramine. Received 4.3 g (12.3 mmol) of product (II) (79%), so pl. 197-199 ° C. R _f 0.25 (spot detection - exposure to the developed plate of natural light). Mass spectrum, m / z: 351, [M] ⁺ . ¹ H NMR spectrum (DMSO-d ₆ , δ, ppm, J / Hz): 1.16 (3H, s, 3a-CH3), 1.31 (3H, s, 3b-CH3), 2.81 (3H, s, 1-CH3), 6.03 (1H, d, J 10.4, 3′-H), 6.80 (1H, d, J 8.3, 7-H), 7.05 (1H, m, J 8.0, 6′-H), 7.22 (1H, d, J 10.3, 4′-H), 7.58 (1H, dd, J 7.6 / 1.5. 6-H), 7.64 (1H, d, 1.5, 4-H), 7.74 (1H, dd, J 8.0 / 1.7, 5′-H), 7.76 (1H, dd, J 8.0 / 1.7, 7′-H), 9.77 (1H. S, 5 - CHO). Found (%): C, 68.38; H, 5.23; N, 8.07; O, 18.32. C ₂₀ H ₁₈ N ₂ O ₄ . Calculated (%): C, 68.56; H, 5.18; N, 8.0; Oh, 18.27. The spectral-kinetic characteristics (II) are shown in Table 1.

Example 3. 5,6′-diformyl-1,3,3-trimethylindolin-2-spiro-2′-2H-chromene (III).

Compound (III) was prepared analogously to (I) (Example 1) from 5 g (15.5 mmol) of 1,2,3-trimethyl-6'-formylspiro (indolino-2,2 '- [2H] chromene) and 4.6 g (32.8 mmol) of hexamethylenetetramine for 1.5 hours. The precipitate was filtered off. The mother liquor was slowly alkalinized with a 1 M potassium hydroxide solution to pH 7, then the product was extracted with methylene chloride 2 times. The organic phases were dried over sodium sulfate, then the solvent was removed in vacuo. Next, the combined extracts and the filtrate were chromatographed on a small layer of silica gel, eluent - petroleum ether (bp. 40-70 ° С) - methylene chloride (1: 3, by volume). Received 4.2 g (12.6 mmol) of product (III) (77%), so pl. 164-166 ° C. R _f 0.20 (spot detection - exposure to the developed plate of natural light). Mass spectrum, m / z: 334, [M] ⁺ . ¹ H NMR Spectrum (DMSO-d ₆ , δ, ppm, J / Hz): 1.15 (3H, s, 3a-CH3), 1.27 (3H, s, 3b-CH3), 2.81 (3H, s, 1-CH3), 5.95 (1H, d, J 10.3, 3′-H), 6.79 (1H, d, J 8.3, 7-H), 6.91 (1H, m, J 8.3, 8′-H), 7.22 (1H, d, J 10.3, 4′-H), 7.64 (1H, d, J 1.7, 4-H), 7.71 (1H, dd, J 8.6 / 2.1, 7′-H), 7.76 (1H, dd J 8.1 / 1.7, 6-H), 7.82 (1H, d, 2.0, 5′-H), 9.77 (1H, s, 5-CHO), 9.83 (1H, s, 6′-CHO). Found (%): C, 75.35; H, 5.83; N, 4.07; O, 14.75. C ₂₁ H ₁₉ NO ₃ . Calculated (%): C, 75.66; H, 5.74; N, 4.2; Oh, 14.40. The spectral-kinetic characteristics (III) are shown in Table 1.

Table 1. Spectral-kinetic characteristics of spiropyran derivatives (I-III) in solution. Compound Solvent λ _A , nm λ _B , nm ΔD ^ph k _BA ^then , with ^-1 t _1/2 , c I Ethanol 328 570 0.85 0.12 40 Toluene 318 585 sq., 625 0.90 0.24 13 II Ethanol 325 580 0.7 0.48 fifty Toluene 317 600 square, 640 0.45 0.84 5 III Ethanol 325 57 0.9 0.39 60 Toluene 317 580 sq., 620 0.23 1.64 2

Claims (2)

1. 5-Formyl-substituted formulas indoline spirobenzopyranes of the General formula

where R ₁ , R ₂ is Alk or c-Alk;
R ₃ - CHO or NO ₂ group (electron-acceptor substituent) with photochromic properties. 2. The method of obtaining 5-formyl-substituted indoline spirobenzopyranes, characterized in that the spiropyrans of the General formula

where R ₁ , R ₂ and R ₃ have the above meanings, are subjected to direct selective formylation at position 5 in a trifluoroacetic acid medium with urotropine (hexamethylenetetramine) at a boiling point of the mixture in an inert atmosphere for 1-1.5 hours.