A method for synthesizing a tervalent tetraaryl iron porphyrin from pyrrole and aromatic aldehyde and divalent iron salt

Abstract

The application discloses a method for synthesizing tervalent tetraaryl iron porphyrin from pyrrole, aromatic aldehyde and ferrous salt, which comprises the following steps: adding anhydrous aluminum chloride, aromatic aldehyde, pyrrole and ferrous salt into DMF under stirring, and then heating and refluxing the reaction mixture for 0.5 hours under nitrogen; removing the nitrogen and continuing to heat the reaction mixture for a certain time; stopping the reaction; cooling the reaction mixture; and placing the reaction mixture at 273K overnight; and finally filtering the reaction mixture to obtain the iron porphyrin.

Description

Technical Field

[0001] This invention relates to a method for synthesizing trivalent tetraaryliron porphyrin from pyrrole, aromatic aldehydes, and divalent iron salts. In particular, it relates to a method for synthesizing tetraaryliron porphyrin in one step using aromatic aldehydes, pyrrole, and ferrous chloride as raw materials in a DMF solvent with anhydrous aluminum trichloride as a catalyst. This method belongs to the field of organic synthesis. Background Technology

[0002] Iron porphyrin is a substance widely found in the human and animal bodies. Iron porphyrin, derived from heme, can be extracted from animal blood. In animals, its main function is as an oxygen carrier and activator. In industrial production and daily life, iron porphyrin is primarily used as a catalyst for chemical oxidation and electro- and photo-oxidation. Tetraaryl iron porphyrin is commonly used as a catalyst. Currently, the chemical synthesis methods for tetraaryl iron porphyrin reported in literature and patents are generally based on the basic reaction of tetraarylporphyrin as a raw material with ferrous salts, as reported by Adler et al. (J. Inorg. Nucl. Chem., 1970, 32, 2443). The chemical processes involved are as follows:

[0003]

[0004] During the reaction, ferrous ions coordinate with tetraarylporphyrin to form a highly unstable ferrous porphyrin intermediate, which then rapidly transforms into a stable trivalent ferrous porphyrin. Patent CN103880851B discloses a method for producing porphyrin iron on an industrial scale via a continuous process, using tetraarylporphyrin as a raw material and reacting it with ferrous salts. The biggest drawback of this reaction is the high cost of tetraarylporphyrin, the raw material used to synthesize porphyrin iron. Furthermore, during the reaction, the product trivalent ferrous porphyrin readily undergoes a dimerization reaction to form a byproduct, diferrous porphyrin. The trivalent ferrous porphyrin and diferrous porphyrin are mixed together and need to be separated to obtain pure trivalent ferrous porphyrin.

[0005] Existing literature also reports one-step synthesis of zinc porphyrins from aryl aldehydes, pyrroles, and zinc salts. Badger et al. reported a one-step synthesis of zinc porphyrins from aryl aldehydes, pyrroles, and zinc salts in an autoclave (Australian J Chem, 1964, 19, 1028).

[0006]

[0007] However, this reaction condition cannot be used to prepare iron porphyrin. In propionic acid solvent and under high temperature and high pressure conditions, ferrous salts will be rapidly converted into ferric salts, and ferric salts cannot form iron porphyrin.

[0008] Given that zinc porphyrin can be replaced by iron salt to obtain iron porphyrin (Chemical Technology, 2000, 8, 1; Journal of Shenyang University of Technology, 2010, 60; Chemical Research and Application, 2012, 24, 154), patent CN1238355C discloses a reaction in which porphyrin zinc and porphyrin mixture are obtained from aryl aldehydes, pyrroles, and zinc salts without the use of an autoclave, and then porphyrin iron is synthesized by reacting the porphyrin zinc and porphyrin mixture with ferrous chloride.

[0009]

[0010] In the above process, the intermediate products zinc porphyrin and porphyrin need to be obtained through a separation process. The propionic acid solvent used in the first step is an organic acid with strong corrosiveness. In addition, if iron salt is directly added to the propionic acid system, iron porphyrin cannot be obtained. Summary of the Invention

[0011] To address the shortcomings of existing technologies that lack a one-step method for synthesizing iron porphyrin from aldehydes, pyrroles, and iron salts, requiring either an oxidative metallization reaction of expensive tetraarylporphyrins with ferrous salts or a metal substitution reaction of expensive tetraarylzinc porphyrins with ferrous salts, the present invention aims to provide a one-step method for synthesizing tetraaryl iron porphyrin from basic organic raw materials aryl aldehydes and pyrroles with inorganic ferrous salts, and to obtain high-purity tetraaryl iron porphyrin in high yield without the need for complex separation methods. This method is easily scalable for industrial production.

[0012] The reaction raw materials selected for this invention are simple organic raw materials aromatic aldehydes and pyrroles, as well as the inorganic salt ferrous chloride. The reaction solvent is DMF, and the catalyst is the aprotic inorganic acid anhydrous aluminum trichloride.

[0013] The chemical reaction upon which this invention is based is as follows:

[0014]

[0015] The aryl Ar group can be a benzene ring or an aromatic heterocycle such as pyridine, pyrrole, furan, naphthalene, or quinoline.

[0016] The substituent R on the aryl Ar group can be an alkyl substituent such as methyl, ethyl, or propyl, or a halogen substituent such as chlorine, bromine, or iodine. It can also be an oxygen-containing substituent such as methoxy, ethoxy, hydroxyl, or carboxyl, or a nitrogen-containing substituent such as amino, dimethylamino, or nitro.

[0017] The operation process for implementing this invention is as follows: DMF is added to a commonly used reflux stirred reactor at room temperature, stirring is started, and anhydrous aluminum trichloride, aryl aldehyde, pyrrole, and ferrous salt are added sequentially. After heating under nitrogen gas and reflux for 0.5 hours, the nitrogen gas is removed, and heating is continued for a certain period of time until the reaction is stopped. The mixture is then cooled and placed at around 273K overnight, and filtered to obtain porphyrin iron purple crystals.

[0018] The molar ratio of aryl aldehyde, pyrrole, ferrous salt and anhydrous AlCl3 is 1-1.5:1-1.5:1-5:1-5, with the preferred ratio being 1:1:1.5:1.5.

[0019] The molar ratio of pyrrole to DMF is 1:500-5000, with a preferred ratio of 1:1000;

[0020] The reaction time is 0.5-3 hours, with the preferred reaction time being 1 hour.

[0021] The reaction requires adding all reactants at room temperature before heating to reflux. If the reactants are added after reflux, or if the ferrous salt is added after reflux, the desired product will not be obtained, or the product yield will be reduced.

[0022] The technical solution of this invention involves the simultaneous occurrence of the condensation of aromatic aldehydes and pyrrole, and the metallization of the condensation product with ferrous ions. This transforms the two-step reaction of the existing technology for synthesizing tetraarylferroporphyrins from aromatic aldehydes and pyrrole into a one-step reaction. Simultaneously, ferrous ions act as a template in the condensation process of aromatic aldehydes and pyrrole, thereby increasing the condensation yield. Anhydrous AlCl3, an aprotic acid, is used as an acidic catalyst, which promotes the condensation of aromatic aldehydes and pyrrole while avoiding the defect of ferrous ions transforming into trivalent ferric ions (which cannot undergo metallization with porphyrin) under proton conditions. The introduction of nitrogen gas ensures the presence of divalent ferric ions. The iron salt is not converted into ferric iron before the reaction; the acidic environment provided by AlCl3 can also prevent the product tetraaryliron porphyrin from further reacting into the byproduct bistetraaryliron porphyrin iron dimer; the use of DMF as a solvent can dissolve anhydrous AlCl3, which is beneficial to the catalytic performance of AlCl3 on the condensation of aromatic aldehydes and pyrroles. The difference in the solubility of DMF for organic hydrocarbons and metal compounds allows tetraaryliron porphyrin to crystallize out at low temperature. During the reaction, various intermediate impurities formed by the condensation of aromatic aldehydes and pyrroles will not precipitate with the product, making the separation of the product tetraaryliron porphyrin simple.

[0023] Compared with the prior art, the technical solution of the present invention brings the following beneficial technical effects:

[0024] 1) Compared with the existing technology of synthesizing tetraaryl iron porphyrin using porphyrin as raw material, the aromatic aldehyde and pyrrole used in this invention are more economical and readily available than porphyrin, and can effectively avoid the formation of bis-iron porphyrin byproducts by further dimerization of the product tetraaryl iron porphyrin, thereby improving product purity and simplifying the separation process.

[0025] 2) Compared with the existing technology of synthesizing tetraaryl iron porphyrin from aromatic aldehydes and pyrroles, the present invention only requires one reaction step, does not require special equipment, reduces reaction steps, and the product yield can reach up to 57% under preferred conditions. At the same time, it can avoid the large-scale use of corrosive organic acids and has good environmental benefits.

[0026] 3) The technical solution of the present invention has simple steps and is easy to operate, meeting the requirements of industrial production. Example

[0027] The following examples are intended to further illustrate the content of the present invention, rather than to limit the scope of protection of the claims. Unless otherwise specified, the raw materials involved in the examples are all commercially available conventional raw materials.

[0028] Example 1:

[0029] 500 mL of DMF was added to a stirred reactor equipped with a reflux condenser. Then, 0.75 mol of anhydrous aluminum trichloride, 0.5 mol of benzaldehyde, 0.5 mol of pyrrole, and 0.75 mol of ferrous chloride were added sequentially with stirring. Nitrogen gas was introduced and the mixture was heated under reflux for 0.5 hours. The nitrogen gas was then removed and the mixture was heated for another 0.5 hours. The reaction was then stopped, the temperature was lowered, and the mixture was left to stand overnight at 273 K. The mixture was then filtered to obtain tetraphenylporphyrin iron purplish-brown crystals with a yield of 57%.

[0030] Example 2:

[0031] 1800 mL of DMF was added to a stirred reactor equipped with a reflux condenser. Then, 1 mol of anhydrous aluminum trichloride, 0.8 mol of 3-methylpyridine carboxaldehyde, 0.6 mol of pyrrole, and 1.5 mol of ferrous chloride were added sequentially with stirring. Nitrogen gas was introduced and the mixture was heated under reflux for 0.5 hours. The nitrogen gas was then removed and the mixture was heated for another 0.7 hours. The mixture was then cooled and placed at 273 K overnight. The mixture was filtered to obtain tetra(3-methylpyridine)porphyrin iron purplish-brown crystals with a yield of 50%.

[0032] Example 3:

[0033] 2800 mL of DMF was added to a stirred reactor equipped with a reflux condenser. Then, 1.2 mol of anhydrous aluminum trichloride, 0.8 mol of 2-ethylpyrrole carboxaldehyde, 0.7 mol of pyrrole, and 2 mol of ferrous chloride were added sequentially with stirring. The mixture was heated under nitrogen and refluxed for 0.5 hours. The nitrogen was then removed, and heating continued for another 1.5 hours. The mixture was cooled and placed at 273 K overnight. Filtering yielded tetra(2-ethylpyrrole)porphyrin iron purplish-brown crystals, with a yield of 32%.

[0034] Example 4:

[0035] 1500 mL of DMF was added to a stirred reactor equipped with a reflux condenser. Then, 0.75 mol of anhydrous aluminum trichloride, 0.75 mol of 5-chloro-1-naphthaldehyde, 0.75 mol of pyrrole, and 2 mol of ferrous chloride were added sequentially with stirring. The mixture was heated under nitrogen and refluxed for 0.5 hours. The nitrogen was then removed and the mixture was heated for another 1.5 hours. The mixture was then cooled and placed at 273 K overnight. The solution was filtered to obtain tetra(5-chloro-1-naphthylpyridine)porphyrin iron purple crystals with a yield of 53%.

[0036] Example 5:

[0037] 1000 mL of DMF was added to a stirred reactor equipped with a reflux condenser. Then, 1 mole of anhydrous aluminum trichloride, 0.6 mole of 3-bromofuran carbaldehyde, 0.5 mole of pyrrole, and 1.8 mole of ferrous chloride were added sequentially with stirring. Nitrogen gas was introduced and the mixture was heated under reflux for 0.5 hours. The nitrogen gas was then removed and the mixture was heated for another 1.3 hours. The mixture was then cooled and placed at 273 K overnight. The mixture was filtered to obtain tetra(3-bromofuran)porphyrin iron purplish-red crystals with a yield of 45%.

[0038] Example 6:

[0039] 1500 mL of DMF was added to a stirred reactor equipped with a reflux condenser. Then, 0.5 mol of anhydrous aluminum trichloride, 0.7 mol of 5-methoxy-2-quinoline carbaldehyde, 0.5 mol of pyrrole, and 1.2 mol of ferrous chloride were added sequentially with stirring. The mixture was heated under reflux for 0.5 hours, then the nitrogen was removed and heating continued for another 2.5 hours. The mixture was then cooled and placed at 273 K overnight. Filtering yielded tetra(5-methoxy-2-quinoline)porphyrin iron purple crystals, with a yield of 25%.

[0040] Example 7:

[0041] 2500 mL of DMF was added to a stirred reactor equipped with a reflux condenser. Then, 2 moles of anhydrous aluminum trichloride, 0.75 moles of 4-hydroxybenzaldehyde, 0.5 moles of pyrrole, and 2 moles of ferrous chloride were added sequentially with stirring. The mixture was heated under nitrogen and refluxed for 0.5 hours. The nitrogen was then removed and the mixture was heated for another 2 hours. The mixture was then cooled and placed at 273 K overnight. The mixture was filtered to obtain tetra(4-hydroxyphenyl)porphyrin iron, a pale green crystal with a yield of 30%.

[0042] Example 8:

[0043] 2000 mL of DMF was added to a stirred reactor equipped with a reflux condenser. Then, 2.5 mol of anhydrous aluminum trichloride, 0.5 mol of 3-aminobenzaldehyde, 0.5 mol of pyrrole, and 1.5 mol of ferrous chloride were added sequentially with stirring. The mixture was heated under nitrogen and refluxed for 0.5 hours. The nitrogen was then removed and the mixture was heated for another 1.5 hours. The mixture was then cooled and placed at 273 K overnight. The solution was filtered to obtain tetra(3-aminophenyl)porphyrin iron blue crystals with a yield of 18%.

[0044] Example 9:

[0045] 1800 mL of DMF was added to a stirred reactor equipped with a reflux condenser. Then, 2 mol of anhydrous aluminum trichloride, 0.6 mol of 4-carboxybenzaldehyde, 0.5 mol of pyrrole, and 2.2 mol of ferrous chloride were added sequentially with stirring. The mixture was heated under nitrogen and refluxed for 0.5 hours. The nitrogen was then removed and the mixture was heated for another hour. The mixture was then cooled and placed at 273 K overnight. The mixture was filtered to obtain tetra(4-carboxyphenyl)porphyrin iron purple crystals with a yield of 25%.

[0046] Example 10:

[0047] 1500 mL of DMF was added to a stirred reactor equipped with a reflux condenser. Then, 0.8 mol of anhydrous aluminum trichloride, 0.6 mol of 4-nitrobenzaldehyde, 0.5 mol of pyrrole, and 2.5 mol of ferrous chloride were added sequentially with stirring. The mixture was heated under nitrogen and refluxed for 0.5 hours. The nitrogen was then removed, and heating continued for another 0.3 hours. The mixture was cooled and placed at 273 K overnight. Filtering yielded tetra(4-nitrophenyl)porphyrin iron purple crystals, with a yield of 15%.

Claims

1. A method for synthesizing trivalent tetraaryliron porphyrin from pyrrole, aromatic aldehydes, and divalent iron salts, characterized in that: Using aromatic aldehydes, pyrroles, and ferrous chloride as raw materials, trivalent tetraaryliron porphyrin was synthesized in one step in DMF solvent with anhydrous aluminum trichloride as catalyst. The reaction process was as follows: DMF was added to a reflux stirred reactor at room temperature, stirring was started, and anhydrous aluminum trichloride, aryl aldehyde, pyrrole, and ferrous salt were added sequentially. Nitrogen gas was introduced and the reactor was heated under reflux for 0.5 hours. After the nitrogen gas was removed, the reactor was heated for a certain period of time, the reaction was stopped, the temperature was lowered, and the reactor was placed at around 273 K overnight. The crystals of trivalent tetraaryliron porphyrin were obtained by filtration. Aromatic aldehydes have the following structures: ； Trivalent tetraaryl iron porphyrin has the following structure: ； The aryl Ar group can be a benzene ring, pyridine, pyrrole, furan, naphthalene, or quinoline; The substituent R on the aryl Ar is methyl, ethyl or propyl, or chlorine, bromine or iodine, or methoxy, ethoxy, hydroxy or carboxyl, or amino, dimethylamino or nitro.

2. The method for synthesizing a tetraaryl iron porphyrin according to claim 1, characterized in that: The molar ratio of aryl aldehyde, pyrrole, ferrous salt and anhydrous AlCl3 is 1~1.5:1~1.5:1~5:1~5.

3. The method for synthesizing trivalent tetraaryl aryl porphyrin from pyrrole, aromatic aldehyde, and divalent iron salt according to claim 1, characterized in that: The molar concentration of pyrrole in DMF is 1 / 500 to 1 / 5000.

4. The method for synthesizing trivalent tetraaryl aryl porphyrin from pyrrole, aromatic aldehyde, and divalent iron salt according to claim 1, characterized in that: The reaction time is 0.5 to 3 hours.

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