CS265186B1 - A method of heterogeneous preparation of metalloporphyrins - Google Patents

Abstract

This is a heterogeneous two-phase method for the preparation of metalloporphyrins of the general formula I, where R^ is hydrogen, alkyl with one to three carbon atoms, phenyl, naphthyl, furyl, pyridyl, substituents and R9 are hydrogen, alkyl with one to three carbon atoms, vinyl, further CH2COOR and CH2CH2COOR, where R is alkyl with one to four carbon atoms and further CH/OH/CH3, CHO or COCH3 and M is a monovalent to tetravalent metal cation, characterized in that the porphyrin of the general formula II, in which the substituents R1 to R9 have the same meaning as in formula I, is metalated in a heterogeneous two-phase environment of a salt of the corresponding metal of the general formula III, where X represents an acetate, halogen, nitrate, sulfate, oxalate, formate anion, m takes on the value 1 to 4, M represents a monovalent to tetravalent metal cation, in an organic solvent at a temperature of 25 to 150 °C, with the liquid phase either being a solution of porphyrin and the salt forming the solid phase, or the salt being in solution and the porphyrin forming the solid phase.

Description

The present invention relates to a heterogeneous process for preparing metalloporphyrins.

Metalloporphyrins belong to substances with the most important biological activity, eg iron complexes form hemin, magnesium complexes form chlorephyl, cobalt complexes form vitamin B · ^ '

Metalloporphyrins (MPs) are an essential component of various biological systems, such as hemoproteins or photosynthetic systems, and important biocatalysts. In synthetic organic chemistry, MPs have been used as catalysts in a number of oxidation reactions, eg, olefin epoxidation, alkane hydroxylation (J. Chem. Soc., Perkin Trans. 2, 1985, 1735; J. Am. Chem. Soc. 108 ,

281 (1986)), possibly attempting to mimic the enzymatic activity of cytochrome p-450 (J. Chem. Soc. 1986, 1743).

Methods for preparing MPs depend primarily on the nature of the complex metal and also to a lesser extent on the type of porphyrin. Commonly used for metalation are methods where the metal cation and porphyrin are part of a single phase (solution). Metallization of porphyrides in a two-phase system (water, oil) has been described using long-chain carboxylic acids, thiols and phenols as the phase transfer catalyst (J. Chem. Soc., Perkin Trans. 2, 1987, 287). New J. Chem., 10, 91 (1986)). However, this method is not preperatively very advantageous because of its experimental design.

Another method of preparing MP is described by the Canadian authors (Can. J. Chem. 56, 1084 (1978)). Metalization proceeds as a heterogeneous reaction wherein porphyrin is present in solution and the metal is in the insoluble form of a metal powder or oxide. A complicating factor is in some cases the considerable adsorption of MP formed on the metal or oxide surface, as well as the slow course for organic solvent-soluble porphyrins and difficult separation of MP and starting porphyrin.

The present invention provides a heterogeneous process for the preparation of the metalloporphyrins of formula (I)

where r! is hydrogen, alkyl of one to three carbon atoms, phenyl, naphthyl, furyl, pyridyl, substi2 9-substituent R to R are hydrogen, alkyl having one to three carbon atoms, vinyl, furthermore Cl-COOR and CH ₂ CH ₂ COOR, R is alkyl of one to four carbon atoms, CH / OH / CH ₃ , CHO or COCH 3 and M is a monovalent to tetravalent metal cation, characterized in that the porphyrin of formula II

(II)

9 in which the substituents R to R have the same meaning as in formula I, are metallized in a heterogeneous biphasic medium of the salt of the corresponding metal of formula III

ΜX (111) mn where X represents acetate, halogen, nitrate, sulphate, oxalate, formate anion, m is 1 to 2, n is 1 to 4, M is a monovalent to tetravalent metal cation, in an organic solvent at a temperature of 25 to 150 ° C, the liquid phase being either a porphyrin solution and a salt forming a solid phase, or a salt in solution and the porphyrin forming a solid phase.

The metal cation may be the following metals: Ag, Pt, Pd, Ni, Co, Cu, Fe, Zn, Mg, Cd, Sn,

Hg, V, Pb.

As the type XI compound, it is advantageous to use acetate of the respective metal (the reaction proceeds faster than with other anions), or a mixture of the metal halide, sulphate or nitrate with an excess of sodium acetate. The reaction is usually carried out by dissolving the porphyrin in an organic solvent, preferably benzene, toluene, dioxane, chloroform, methylene chloride, 1,2-dichloroethane, or a mixture thereof, adding a salt of the appropriate metal to form a complex with the porphyrin. The reaction mixture is mixed with a magnetic stirrer and monitored for metallization by UV-VIS spectroscopy or thin layer chromatography, the temperature being from room temperature to the boiling point of the solvent used. The reaction usually proceeds very rapidly, often after 10 min the free base of porphyrin is no longer present. A great advantage is also the quantitative course of the reaction, the metalloporphyrin is obtained in high purity. In addition, the heterogeneous reaction process makes the product very easy to isolate. The reaction is carried out by suctioning off the salt, washing it with a solvent and evaporating the filtrate on a rotary evaporator to give a metalloporphyrin which, by its purity, satisfies the requirements of the analytical sample. A great advantage of the novel process for the preparation of metalloporphyrins compared to the approaches used so far is, in particular, simplicity, ease of isolation of the practically quantitative product and ease of availability of the raw materials used.

Another method of preparation according to the invention is that the liquid phase is a solution in glacial acetic acid or pyridine and the porphyrin is metallized undissolved in the solid phase. This process can also be applied to the preparation of water-soluble metalloporphyrins, e.g., meso-tetra (p-sulfophenyl) porphyrin metallo-derivatives. The arrangement of the heterogeneous metallation is such that in the solvent used the respective salt is well soluble (usually glacial acetic acid or pyridine), while the porphyrin derivative forms a solid phase. Metallization is carried out with vigorous stirring at temperatures of 40 to 100 ° C.

The present invention is further illustrated by the following non-limiting examples.

Example 1

Preparation of the copper complex of 5,10,15,20-tetrafenyl-21H, 23H-porphyrin (ie CuTPP).

5,10,15,20-tetrafenyl-21H, 23H-porphyrin (1.229 g; 2 mM) was dissolved in 100 mL of chloroform and 1.996 5 g (10 mM) of copper acetate was added. While stirring with a magnetic stirrer, it was heated to reflux and the kinetics of the metalation by UV-VIS spectra and thin layer chromatography on silica gel in benzene-petroleum ether (1: 1) was monitored. Both the anhydrous salt and the copper (II) acetate with crystalline water can be used for the metallation without significantly altering the reaction. After 10 min reflux, the starting porphyrin was no longer detected. After cooling to room temperature, the salt was filtered off with suction, washed with 10 ml of chloroform, and the filtrate was evaporated to dryness on a rotary evaporator. The product (CuTTP) was obtained in virtually quantitative yield (1.35 g; 99.8%).

Its chromatographic (TLC, HPLC) and spectral characteristics are identical to the authentic sample (Aldrich Company).

Example 2

Preparation of CuTPP by the procedure of Example 1 but substituting chloroform for dioxane, heating for 15 min at 100 ° C, yield 97%.

Example 3

Preparation of CuTPP by the procedure of Example 1, but with the substitution of copper acetate for the same molar amount of copper chloride, reaction time at reflux of chloroform 30 min, product yield 95%.

Example 4

Preparation of CuTPP according to Example 1 but substituting copper acetate for 10 molar equivalents of copper sulfate, reflux in chloroform for 5 h, yield 90%.

Example 5

Preparation of CuTPP according to Example 1 but substituting copper acetate for a mixture of 3 molar equivalents of copper nitrate and 10 molar equivalents of sodium acetate. Reflux 10 min, yield 87%.

Example 6

Preparation of CuTPP according to the procedure of Example 1 but substituting chloroform for benzene, toluene or a mixture thereof, reflux for 3 h. After cooling, the salt is filtered off with suction, washed with chloroform (3x20 ml), the combined filtrates are evaporated. 95% of the product was obtained.

Example 7

Preparation of cobalt complex 5,10,15,20-tetrafenyl-21H, 23H-porphyrin (CoTPP): 5,10,15,20-tetrafenyl-21, H, 23H-porphyrin (0.614 8 g; 1 mM) was dissolved in 50 ml of 1,2-dichloroethane and 0.885 g (5 mM) of cobalt acetate are added. Reflux for 30 min, after cooling to aspirate the cobalt chloride, wash with 20 ml of the above solvent, the combined filtrates are evaporated to dryness on a rotary evaporator; 0.67 g (99%) of a product with chromatographic and spectral characteristics being identical to an authentic sample was obtained.

Example 8

Preparation of ferric complex: 5,10,15,20-tetrafenyl-21H, 23H-porphyrin chloride (Fe / III) C1TPP 5,10,15,20-tetrafenyl-21H, 23H-porphyrin (0.614 8 g; 1 mM) was dissolved in 100 ml of chloroform, 0.973 g (6 mM) of anhydrous ferric chloride was added. Reflux for 3 h, then cool the reaction to room temperature, aspirate the salt, wash with 10 mL of chloroform, concentrate the combined filtrates to dryness; 0.69 g (98%) of Fe / III / CITPP was obtained, the characteristics of which were identical to the authentic sample.

Example 9

Preparation of the manganese, nickel, zinc and palladium complex of 5,10,15,20-tetrafenyl-21H, 23H-porphyrin by the procedure of Example 1, but with the substitution of copper acetate for the acetate of the above metal. The products - MnTPP, NiTPP, ZnTPP, PdTPP were obtained in a yield of 93 to 98%, characteristics identical to authentic samples.

Example 10

Copperorphyrin tetraethyl ester: Nickel coproporphyrin tetraethyl ester (76.69 g;

0.1 mM) was dissolved in 30 ml 1,2-dichloroethane and then 10 molar equivalents (0.176 8 g; 1 mM) of nickel acetate were added. The reaction mixture was stirred with a magnetic stirrer and refluxed for 1 h. The salt was filtered off, washed with 1,2-dichloroethane, the combined filtrates were evaporated on a rotary evaporator. The product was obtained in 93 výtěž yield, characteristics consistent with a sample prepared according to literature procedures (J. E. Falk, Porfyrins and metalloporfyrins. Elsevier 1964, pp. 30, 115). The procedure is suitable for both Isomer I and III.

Example 11

Protoporphyrin IX dimethyl ester complex: Protoporphyrin IX dimethyl ester (59.1 mg, 0.1 mm) was dissolved in 25 mL chloroform, 0.173 g (1 mM) of manganese acetate was added, the reaction mixture was refluxed for 3 h. After cooling to room temperature, the salt was The filtrate was evaporated on a rotary evaporator. Yield of product 95 i.

Example 12

The zinc complex of protoporphyrin IX dimethyl ester prepared by the procedure of Example 11, but with a replacement of manganese acetate for 0.183 5 g of zinc acetate. The product was obtained in 96% yield.

Example 13

Lead complex of uroporphyrin I octamethyl ester: Uroporphyrin I octamethyl ester (94.3 mg; 0.1 mM) (the method is suitable for all uroporphyrin isomers) was dissolved in 40 ml of chloroform and added 10 molar equivalents of lead bromide (0.367 g, i.e. 1 mM) and refluxed for 5 h.

After cooling to room temperature, the salt was aspirated, washed, and the combined filtrates were evaporated on a rotary evaporator; product obtained in 90% yield.

Example 14

Cobalt and cadmium uroporphyrin I tetramethyl ester complex was prepared according to the procedure of Example 13, but lead bromide was exchanged for 0.248 g of cobalt acetate and cobalt acetate, respectively.

0.230 g cadmium acetate. The products were obtained in yields of 90 and 94%.

Example 15

Copper deuteroporphyrin IX dimethyl ester: Deuteroporphyrin IX dimethyl ester (53.9 mg; 0.1 mM) was dissolved in 30 ml of a 1: 1 chloroform-dioxane mixed solvent and 0.199 g of copper acetate was added. The reaction was performed with magnetic stirring at reflux for 30 min. After cooling to room temperature, the salt was aspirated, washed with chloroform, and the combined filtrates were evaporated on a rotary evaporator; product obtained in 96% yield.

Example 16

Copper meso-tetra (p-sulfophenyl) porphyrin (CuTPS4) I 0.108 4 g (1 mM) of E @ + TPP (SO4 Na) are suspended in 20 ml of glacial acetic acid, 5 mM - 0.998 g of copper acetate are added and Methanol is carried out under magnetic stirring and heating at 80 ° C for 3 h. After cooling to room temperature, the product was aspirated, washed with 5 ml of glacial acetic acid and then with ethanol and dried. Yield CuTPPS ≥ 95%. For C ^ HHj ^S ^O- ^Na ^C Cu calculated:

C, 48.73; H, 2.23; N, 5.17; S, 11.83; found: 48.54% C, 2.46% H, 5.09% N, 11.76% S. The spectral characteristics of the product also agree with an authentic sample prepared according to Can. Chem. 56, 1084 (1978).

Example 17

Copper meso-tetra (p-sulfophenyl) porphyrin complex (CuTPPS ₄ ) prepared according to the procedure of Example 16, but with solvent exchange: glacial acetic acid was replaced with pyridine.

Claims (1)

A process for the heterogeneous preparation of metalloporphyrins of the general formula 1 wherein R ¹ is hydrogen, alkyl of one to three carbon atoms, phenyl, naphthyl, furyl, pyridyl, substituents R 1 to R 2 are hydrogen, alkyl of one to three carbon atoms, vinyl. Wherein R is alkyl of one to four carbon atoms and further CH / OH / CH3, CHO or COCH3 and M is a monovalent to tetravalent metal cation, characterized in that the porphyrin of formula II In which the substituents R to R have the same meaning as in formula I, are metallized in a heterogeneous biphasic medium of the salt of the corresponding metal of formula III Μ X (III) 'mn where X represents acetate, halogen, nitrate, sulphate, oxalate, formate anion, m is 1 to 2, n is 1 to 4, M represents a monovalent to tetravalent metal cation, in an organic solvent at temperature 25 to 150 ° C, the liquid phase being either a porphyrin solution and a salt forming a solid phase, or a salt in solution and the porphyrin forming a solid phase.