RU2479586C1 - Method of producing non-metal tetraazachlorins - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: described is a novel method of producing non-metal tetraazachlorins of general formula

or

or

R²=R³=R⁴=R⁵=H, Br, CI; R³=R⁴=R⁵=H, R²=NO₂, PhSO₂, PhS; R²=R⁴=R⁵=H, R³=NO₂, PhSO₂, t-Bu; R²=R⁵=H, R³=R⁴=PhS; by mixed condensation of tetramethylsuccinonitrile (TMSN) with corresponding 1,2-dinitriles of unsaturated aliphatic or aromatic acids in the presence of indium chloride, with molar ratio TMSN:dinitrile:indium chloride of 1-5:1:1 and catalytic amounts of ammonium molybdate in quinoline at 230-238°C, followed by demetallisation of the intermediate indium complexes with hydrochloric acid.

EFFECT: method considerably increases output of end products.

1 cl, 12 ex, 1 tbl

Description

The present invention relates to chemistry and chemical technology, and more specifically to the synthesis of representatives of a new class of functional dyes - tetraazanalogs of chlorin, namely, alkyl- and aryl-substituted and triarene-condensed, methyl-free tetraazachlorins.

Tetraazachlorins (TAX) are more resistant to oxidation than chlorins, they have long-wavelength absorption in the near IR region and are promising as a new class of functional dyes, which are currently of great practical interest, for example, for creating solar cells.

Studies of the photodynamic activity of synthesized non-metallic TAXs have shown that these compounds represent a new class of effective near-infrared photosensitizers for photodynamic therapy (PDT), which can be used to treat deep tumor tissues using PDT [RF Patent 2278119, C07D 487/22, 2006 ].

Due to the molecular structure, in particular the presence of two Quaternary carbon atoms with metal groups outside the plane of the molecule, β, β, β ', β'-tetramethyltetraazachlorins have good solubility in organic solvents and in polymer matrices.

Limeless TAX can be obtained by mixed condensation of tetramethylsuccinonitrile (TMSN) with dinitriles in boiling dimethylaminoethanol in the presence of lithium dimethylaminoethylate [RF Patent No. 2188200, C07D 487/22, 2002, prototype]. The main disadvantage of this method is the low yield of the target products (from 1.5 to 4%).

An object of the present invention is to provide a method for the synthesis of non-methylated TAX with improved yield.

The problem is solved in that the metalless tetraazachlorins of the general formula, for example:

;

;

R ² = R ³ = R ⁴ = R ⁵ = H, Br, Cl;

R ³ = R ⁴ = R ⁵ = H, R ² = NO ₂ , PhSO ₂ , PhS;

R ² = R ⁴ = R ⁵ = H, R ³ = NO ₂ , PhSO ₂ , t-Bu;

R ² = R ⁵ = H, R ³ = R ⁴ = PhS;

obtained by mixed condensation of tetramethylsuccinonitrile (TMSN) with 1,2-dinitriles of unsaturated aliphatic or aromatic acids

, где R-R¹, как указано выше,

where RR ¹ as described above

in the presence of indium chloride in a molar ratio of 1 ÷ 5: 1: 1 and catalytic amounts of ammonium molybdate in quinoline at 230-238 ° C, followed by demetallation of the intermediate indium complexes with hydrochloric acid.

A feature of the method is the intermediate production of indium complexes in mixed condensation with their subsequent demetallation, which also makes it possible to synthesize inaccessible when using the lithium method according to the prototype substituted TAX containing substituents in the β-positions of the pyrrole rings and in different positions of the condensed benzene rings of the macrocycle.

Thus, in the interaction of a mixture of TMSN, phthalonitrile and InCl ₃ in a molar ratio of 3: 1: 1 at 230 ° C in the quinoline in the presence of ammonium molybdate, the indium complex β, β, β ', β'-tetramethyltribenzotetraazachlorin (TBTAX) in a mixture with phthalocyanine India. Attempts to separate this mixture by chromatography were unsuccessful due to the low photostability of the TBTAX indium complex. However, the TBTAX indium complex is easily demetallized upon treatment with concentrated hydrochloric acid even at room temperature. The methyl free TBTAX (yield up to 40.5%) is easily separated from indium phthalocyanine by extraction of the technical product with chlorobenzene, followed by chromatography on silica gel with chloroform. A change in the molar ratio of TMSN to phthalonitrile outside the specified ratio leads to a decrease in the yield of TBTAX.

The reaction of TMSN with 4-tert-butylphthalonitrile under similar conditions yields β, β, β ', β'-tetramethyltri (4-tert-butylbenzo) tetraazachlorin (17.7%), which is not formed using the lithium method. As unsaturated phthalogens, various substituted phthalonitriles, 1,2-dicyanonaphthalene, as well as mono- and disubstituted maleonitriles can be used.

The synthesized compounds in electronic absorption spectra have intense bands in the red and near-IR spectral regions. The introduction of three condensed benzene rings or phenyl substituents into the unsubstituted TAX molecule leads to a significant bathochromic shift of the long-wavelength band Q, which is associated with the expansion of the π-electron system of the macrocycle. Thus, in the absorption spectrum of TBTAX in chloroform in the long wavelength region, an intense Q band is observed, which is split into two components located at 747 and 605 nm (for TAX at 678 and 520 nm). A strong bathochromic shift is observed for β, β, β ', β'-tetramethyltri (3-phenylsulfanylbenzo) tetraazachlorin (781 and 629 nm). Thus, the proposed method makes available compounds with intense electron absorption in the near infrared region, which is of practical interest for their use in various fields of technology.

The present invention is illustrated by the following examples.

Example 1

Tetramethylsuccinonitrile. 10 g of azoisobutyronitrile are boiled in 250 ml of toluene for 10 hours. The reaction mass is cooled, diluted with 300 ml of hexane and left in the refrigerator overnight. The precipitate formed is filtered off, washed with hexane, and dried in air. Get 7.5 g (87%) TMSN with so pl. 156 ° C (hexane).

2,2,3,3-tetramethyl-7,8,12,13,17,18-hexaphenyltetraazachlorin. A mixture of 1.5 g (11.0 mmol) of TMSN, 0.82 g (3.7 mmol) of indium chloride and 0.003 g of ammonium molybdate (MOA) in 5 ml of quinoline is heated to 230 ° C. with stirring. Then, 0.85 g (3.7 mmol) of diphenylmaleodinitrile is added over 10 minutes and stirring is continued at the same temperature for another 10 minutes. Then the reaction mass is cooled to room temperature, diluted with 50 ml of 50% aqueous acetone, the precipitate is filtered off, washed with hot water and dried in air. The dry precipitate is then suspended in 5 ml of hydrochloric acid, stirred for 5 minutes at room temperature, then filtered, washed with water to a neutral pH of the washings and dried in air. The dry precipitate was dissolved in chloroform and chromatographed on silica gel using a mixture of hexane - methylene chloride (1: 1) as an eluent. The pink fraction was collected and 0.39 g (38.2%) of 2,2,3,3-tetramethyl-7,8,12,13,17,18-hexaphenyltetraazachlorine was obtained.

Electronic absorption spectrum, λ _max , nm (log ε), chloroform: 727 (4.93), 689 pl. (4.22), 656 pl. (4.13), 557 (4.43), 488 (4.12), 370 (4.66), 334 (4.67).

Example 2

β, β, β ', β'-tetramethyltribenzotetraazachlorin. A mixture of 1.5 g (11.1 mmol) of TMSN, 0.82 g (3.7 mmol) of indium chloride and 0.003 g of MOA in 5 ml of quinoline is heated with stirring to 230 ° C. Then 0.47 g (3.7 mmol) of phthalonitrile are added in portions over 10 minutes and stirring is continued at the same temperature for another 5 minutes. Next, the reaction mass is cooled to room temperature and processed, as in example 1. The dry precipitate is thoroughly triturated, and then extracted in a Soxhlet apparatus with chlorobenzene. Next, the extract is evaporated in vacuo to a volume of 20 ml and chromatographed on silica gel with chloroform. The blue fraction was collected and 0.26 g (40.5%) of β, β, β ′, β′-tetramethyltribenzotetraazachlorin were obtained.

Electronic absorption spectrum, λ _max , nm (log ε), chlorobenzene: 747 (5.10), 711 (4.51), 677 (4.15), 605 (4.60), 338 (4.83).

Examples 3-9

The synthesis was carried out analogously to example 1, but the process parameters were changed. The reaction conditions and product yield are shown in the Table.

Table Example The molar ratio of TMSN: phthalonitrile: InCl ₃ Temperature ° C Time min Exit, % 3 1: 1: 1 230 10 13.6 four 2: 1: 1 230 10 25.0 5 5: 1: 1 230 10 28,2 6 3: 1: 1 238 40 5.2 7 3: 1: 1 230 5 16.6 8 3: 1: 1 230 10 38.3 9 3: 1: 1 230 fifteen 40.5 10 3: 1: 1 230 thirty 35,4

Example 10

β, β, β ', β'-Tetramethyltri (4-tert-butylbenzo) tetraazachlorin. A mixture of 1.1 g (8 mmol) of TMSN, 0.6 g (2.7 mmol) of indium chloride and 0.003 g of MOA in 5 ml of quinoline is heated with stirring to 230 ° C. Then 0.5 g (2.7 mmol) of 4-tert-butylphthalonitrile is added in portions over 10 minutes and stirring is continued at the same temperature for another 10 minutes. Next, the reaction mass was cooled to room temperature and treated as in Example 1. The dry precipitate was dissolved in chloroform and chromatographed on silica gel using a mixture of hexane - methylene chloride (7: 3) as an eluent. The first blue fraction was collected and 0.11 g (17.7%) of β, β, β ′, β′-tetramethyltri (4-tert-butylbenzo) tetraazachlorin was obtained. Mass spectrum, m / z: 691.95 [M + 1] ⁺ . Found,%: C 75.96; 75.95; H, 7.70; 7.70; N, 15.56; 15.67. C ₄₄ H ₅₀ N ₈ . Calculated,%: 76.49; H, 7.29; N, 16.22.

Electronic absorption spectrum, λ _max , nm (log ε), hexane: 750 (5.28), 712 (4.45), 679 (4.16), 658 (3.81), 602 (4.68), 339 (4.90).

Example 11

β, β, β ', β'-Tetramethyltr (3-phenylsulfanylbenzo) tetraazachlorin. A mixture of 0.88 g (6.4 mmol) of TMSN, 0.47 g (2.1 mmol) of indium chloride and 0.003 g of MOA in 5 ml of quinoline is heated with stirring to 230 ° C. Then, 0.5 g (2.1 mmol) of 3-phenylsulfanylphthalonitrile is added portionwise over 10 minutes and stirring is continued at the same temperature for another 15 minutes. Next, the reaction mass was cooled to room temperature and treated as in Example 1. The dry precipitate was dissolved in methylene chloride and chromatographed on silica gel using a mixture of hexane - methylene chloride (1: 1) as an eluent. The first green fraction was collected and 0.07 g (12.0%) of β, β, β ′, β′-tetramethyltri (3-phenylsulfanylbenzo) tetraazachlorine was obtained. Mass spectrum, m / z: 847.73 [M] ⁺ .

Electronic absorption spectrum, λ _max , nm (log ε), chlorobenzene: 785 (5.06), 744 pl. (4.31), 709 pl. (4.17), 656 pl. (4.26), 632 (4.56), 607 pl. (4.34), 438 pl. (3.87), 333 (4.70).

Example 12

β, β, β ', β'-Tetramethyltri (1,2-naphtho) tetraazachlorin. A mixture of 1.5 g (11.1 mmol) of TMSN, 0.82 g (3.7 mmol) of indium chloride and 0.003 g of MOA in 5 ml of quinoline is heated with stirring to 230 ° C. Then 0.67 g (3.7 mmol) of 1,2-dicyanonaphthalene are added in portions over 10 minutes and stirring is continued at the same temperature for another 5 minutes. Next, the reaction mass is cooled to room temperature and processed, as in example 1. The dry precipitate is thoroughly triturated, and then extracted in a Soxhlet apparatus with chlorobenzene. Next, the extract is evaporated in vacuo to a volume of 10 ml and chromatographed on silica gel with chloroform. The blue fraction was collected and 0.230 g (28.1%) of β, β, β ′, β′-tetramethyltri (1,2-naphtho) tetraazachlorin was obtained.

Electronic absorption spectrum, λ _max , nm (log ε), chlorobenzene: 767 (5.16), 731 (4.40), 694 (4.19), 604 (4.70), 363 (4.74).

Thus, the proposed method allows to obtain, with a yield of up to 40%, metalless tetraazachlorins, which are promising photosensitizers for PDT, as well as key compounds for the synthesis of various metal complexes.

Claims (1)

A method of obtaining a metalless tetraazachlorins of the General formula

or

R ² = R ³ = R ⁴ = R ⁵ = H, Br, Cl;
R ³ = R ⁴ = R ⁵ = H, R ² = NO ₂ , PhSO ₂ , PhS;
R ² = R ⁴ = R ⁵ = H, R ³ = NO ₂ , PhSO ₂ , t-Bu;
R ² = R ⁵ = H, R ³ = R ⁴ = PhS;
consisting in the fact that mixed condensation of tetramethylsuccinonitrile with the corresponding 1,2-dinitriles of unsaturated aliphatic or aromatic acids is carried out in the presence of indium chloride at a molar ratio of tetramethylsuccinonitrile, 1,2-dinitrile and indium chloride 1 ÷ 5: 1: 1 and catalytic amounts of molybdenum in quinoline at 230-238 ° C, followed by demetallation of the intermediate indium complexes formed with hydrochloric acid.