JP4595299B2 - Method for producing porphyrin compound - Google Patents

Description

  The present invention relates to a novel method for synthesizing a porphyrin-based compound having a substituent at the meso position.

  Porphyrins and porphyrin-like compounds are widely used as pigments having various functions, such as hemoglobin heme and photosynthesis chlorophyll in nature. Compounds that use this function are being studied, and their application to light energy, chemical reaction catalysts, chemical sensors, phototherapy, etc. are being studied. Modification of porphyrin molecules is necessary to develop its function, and abundant porphyrin chemistry has been developed and used.

  As a method for synthesizing porphyrin, the most convenient method is to tetramerize pyrrole or a derivative thereof to derive a cyclic porphyrin compound. For example, a method of synthesizing tetraphenylporphyrin by condensing pyrrole and benzaldehyde in propionic acid is well known. In such a synthesis method, a highly interesting compound in which the same group is bonded to four meso positions can be obtained.

  Further, a method for synthesizing a porphyrin compound in which hydroxymethylpyrrole is tetramerized and cyclized to form porphyrinogen, which is oxidized and converted to porphyrin is known as a high yield method. Non-Patent Documents 1 and 2 report a method of synthesizing a porphyrin compound by acid-treating and oxidizing a 2-hydroxymethylpyrrole derivative produced by reducing a pyrrole-2-carboxylic acid ethyl ester derivative with lithium aluminum hydride. Has been. This also yields a highly symmetric compound in which the same groups are bonded to the four meso positions.

On the other hand, introducing a substituent only at one of the four meso positions of the porphyrin may be necessary for the functionalization of the porphyrin. For example, a compound in which a porphyrin ring is bonded to a polymer side chain at a meso position is the most conceivable as a polymer having a porphyrin ring.
A method for synthesizing a monosubstituted porphyrin is a method in which a pyrrole ring is bonded stepwise to produce an asymmetric porphyrin. For example, Non-Patent Document 3 reports a method for synthesizing a mono-substituted product through multi-step steps. In principle, this method can synthesize only one kind of one-substitution product, but it has many disadvantages that it takes many steps, takes time, and lowers the yield.
J. et al. Chem. Soc. Perkin Trans. 1, 3161 (1997) Heterocycles 52, 399 (2000) Org. Lett. 2002, 4, 3807

  Thus, in order to synthesize a porphyrin compound having a substituent at the meso position, it is difficult to synthesize it efficiently because, for example, a multi-step reaction is required.

As a result of intensive studies to solve the above-mentioned problems, the present inventors synthesize porphyrinogen by oxidizing porphyrinogen, by allowing an aldehyde compound to coexist in the system before the oxidation treatment, The inventors have found that a porphyrin compound having a substituent at the meso position can be easily synthesized, and have reached the present invention.
That is, the gist of the present invention is a method for producing a porphyrin compound having a substituent at the meso position, wherein an aldehyde (excluding formaldehyde) is present in the system when the porphyrinogen derivative is oxidized. Exist.

  According to the present invention, a porphyrin compound having a substituent at the meso position can be obtained efficiently.

Hereinafter, embodiments of the present invention will be described in detail.
The present invention is characterized in that when a porphyrinogen derivative is oxidized, an aldehyde (excluding formaldehyde) or an alcohol that can be converted into an aldehyde (excluding formaldehyde) by oxidation is present in the system. This is a method for producing a porphyrin-based compound having a substituent at the meso position.

(Porphyrinogen derivative)
In the present invention, the porphyrinogen derivative is a cyclic tetramer compound of a pyrrole derivative having methylene at the 2-position. Specifically, the following general formula (I)

(Wherein Q ^{1 ′ to} Q ^{8 ′} each independently represent a monovalent group , of which (Q ^{1 ′} and Q ^{2 ′} ), (Q ^{3 ′} and Q ^{4 ′} ), (Q ^{5 'And} Q ^6' ), and (Q ^{7 '} and Q ^8' ) may be bonded to each other to form a ring structure.).

The monovalent group of Q ^{1 ′ to} Q ^{8 ′} is not particularly limited as long as it is a group that does not adversely affect the oxidation reaction. Specifically, a hydrogen atom; a fluorine atom, a chlorine atom, a bromine atom, etc. Cyano group; isocyanato group; isocyanato group; thiocyanato group; isothiocyanato group; mercapto group; hydroxy group; epoxy group; formyl group; sulfonic acid group; carboxyl group; An optionally substituted alkyl group; an optionally substituted cycloalkyl group; an optionally substituted alkenyl group; an optionally substituted cycloalkenyl group; an optionally substituted aryl group; an optionally substituted complex; A cyclic group; an optionally substituted alkoxy group; an optionally substituted alkenyloxy group; an optionally substituted aryloxy group; Shi group; represented by -COOQ ^9; amino group represented by -NQ ¹⁰ Q ^11; acyloxy group represented by -OCOQ ^9; acyl group represented by -COQ ^9; alkylthio group which may be substituted A carboxylic acid ester group; a carbamoyl group represented by —CONQ ¹² Q ¹³ ; a sulfinyl group represented by —SOQ ⁹ ; a sulfonyl group represented by —SO ₂ Q ⁹ ; a sulfone represented by —SO ₃ Q ⁹ An acid ester group; a sulfamoyl group represented by —SO ₂ NQ ¹² Q ¹³ may be mentioned. Among these, an optionally substituted alkyl group; an optionally substituted cycloalkyl group; an optionally substituted alkenyl group; an optionally substituted cycloalkenyl group; an optionally substituted aryl group; An optionally substituted heterocyclic group; an optionally substituted alkoxy group; an optionally substituted alkenyloxy group; an optionally substituted aryloxy group; an optionally substituted alkylthio group; represented by -CONQ ¹² Q ^13; amino group represented by -NQ ¹⁰ Q ^11;; -OCOQ ⁹ acyloxy group represented by; carboxylic acid represented by -COOQ ⁹ ester groups acyl group represented by ⁹ that a carbamoyl group; a sulfinyl group represented by -SOQ ^9; sulfonyl group represented by -SO ₂ Q ^9; sulfonic acid ester represented by -SO ₃ Q ⁹ groups; - The sulfamoyl group represented by O ₂ NQ ¹² Q ^13, 18 or less carbon atoms, preferably those having 12 or less.

Examples of the alkyl group include linear or branched alkyl groups such as methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, sec-butyl group, tert-butyl group, and n-heptyl group. .
Examples of the cycloalkyl group include cyclic alkyl groups such as a cyclopropyl group, a cyclopentyl group, a cyclohexyl group, and an adamantyl group.

Examples of the alkenyl group include linear or branched alkenyl groups such as a vinyl group, a propenyl group, and a hexenyl group.
Examples of the cycloalkenyl group include cyclic alkenyl groups such as a cyclopentenyl group and a cyclohexenyl group.
Examples of the aryl group include a phenyl group and a naphthyl group.

Examples of the heterocyclic group include heterocyclic groups having 1 to 3 hetero atoms such as 2-thienyl group, 2-pyridyl group, 4-piperidyl group, and morpholino group.
Examples of the alkoxy group include linear or branched alkoxy groups such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, a sec-butoxy group, and a tert-butoxy group.

Examples of the alkenyloxy group include linear or branched alkenyloxy groups such as a propenyloxy group, a butenyloxy group, and a pentenyloxy group.
Examples of the aryloxy group include a phenoxy group and a naphthyloxy group.
Examples of the alkylthio group include linear or branched alkylthio groups such as a methylthio group, an ethylthio group, an n-propylthio group, an n-butylthio group, a sec-butylthio group, and a tert-butylthio group.

Examples of Q ⁹ in the acyl group, acyloxy group, carboxylic acid ester group, sulfinyl group, sulfonyl group, and sulfonic acid ester group include an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group. .
The Q ¹⁰ and Q ¹¹ in the amino group, each independently, a hydrogen atom, a hydroxyl group, a hydrocarbon group, a heterocyclic group, an acyl group represented by -COQ ^9, carboxylic acid ester represented by -COOQ ⁹ And a sulfonyl group represented by —SO ₂ Q ⁹ .

Examples of Q ¹² and Q ¹³ in the carbamoyl group or sulfamoyl group independently include a hydrogen atom, a hydrocarbon group, or a heterocyclic group.
The alkyl group, cycloalkyl group, alkenyl group, cycloalkenyl group, aryl group, heterocyclic group, alkoxy group, alkenyloxy group, aryloxy group, alkylthio group and hydrocarbon group are within the range that does not adversely affect the oxidation reaction. Arbitrary substitution may be carried out, and specific examples thereof include groups described as specific examples of Q ^{1 ′ to} Q ^{8 ′} described above.

In addition, (Q ^{1 ′} and Q ^{2 ′} ), (Q ^{3 ′} and Q ^{4 ′} ), (Q ^{5 ′} and Q ^{6 ′} ), and (Q ^{7 ′} and Q ^{8 ′} ) are integrated with each other. Become a propylene group, a butylene group, etc., each of which may be an aliphatic hydrocarbon group that forms a condensed ring with a pyrrole ring, or the formed condensed ring is an aromatic such as a benzene ring or a naphthalene ring It may be a carbocycle, and may be further substituted with a heteroatom to form a heterocyclic group such as a pyrrole ring or a pyridine ring, and among these, an aliphatic carbocycle is preferable. More preferably, it is group represented by the following general formula (II).

Q ^{1 ′ to} Q ^{8 ′} are preferably hydrogen, an alkyl group which may be substituted, or a group represented by the general formula (II).

  The porphyrinogen derivative can be synthesized by a known method such as an acid treatment of a 2-hydroxypyrrole derivative or a condensation reaction of a pyrrole derivative and an aldehyde as represented by the following formula (III). A method of synthesizing the 2-hydroxypyrrole derivative by acid treatment is preferable.

(In the formula, R represents a group corresponding to Q ^{1 ′ to} Q ^{8 ′} of the general formula (I).)
Here, the 2-hydroxypyrrole derivative can be produced by reducing a pyrrolecarboxylic acid ester derivative with a reducing agent such as lithium aluminum hydride, but the ester derivative is not particularly limited, but preferably carbon. It is preferable to use an ester of an alcohol having 1 to 8 carbon atoms, more preferably an ester of an alcohol having 1 to 4 carbon atoms.

In addition, after the reaction is completed, the excess reducing agent is inactivated with an acetate ester, water, or an aqueous solution of an inorganic salt so that the subsequent reaction is not affected.
(Oxidation reaction)
The method for producing a porphyrin-based compound having a substituent at the meso position of the present invention is to oxidize the above porphyrinogen derivative to produce a porphyrin-based compound by adding an aldehyde (excluding formaldehyde) in the oxidation reaction system. It is characterized by being present.

As the aldehyde, an aldehyde represented by the following general formula (IV) can be used.

In the formula, R ¹ is not particularly limited as long as it is a monovalent organic group as described above for Q ^{1 ′ to} Q ^{8 ′} , but preferably a hydrogen atom, a halogen atom, a nitro group, a nitroso group, a cyano group, Substituted with isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, halogenated acyl group, alkyl group, aryl group, or haloalkyl group Linear, branched or cyclic alkyl group which may be substituted; hydrogen atom, halogen atom, nitro group, nitroso group, cyano group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto group , Hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide group A linear, branched or cyclic alkenyl group which may be substituted with an alkyl group, an aryl group, or a haloalkyl group; a hydrogen atom, a halogen atom, a nitro group, a nitroso group, a cyano group, an isocyano group, a cyanato group, Isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide group, alkyl group, aryl group, or aryl optionally substituted by haloalkyl group Groups. More preferably, it is substituted with a hydrogen atom, halogen atom, cyano group, isocyano group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, halogenated acyl group, alkyl group, aryl group, or haloalkyl group. Linear or branched alkyl group having 1 to 13 carbon atoms; hydrogen atom, halogen atom, cyano group, isocyano group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide group , An aryl group that may be substituted with an alkyl group, an aryl group, or a haloalkyl group.

  The content of the aldehyde is not particularly limited, but is preferably 1 mol or more with respect to 1 mol of the porphyrinogen derivative. Further, it is preferably 50 mol or less, more preferably 26 mol or less. When the amount is less than 1 mol, the yield of the porphyrin compound having one substituent at the meso position is deteriorated. When the amount is more than 50 mol, a porphyrin compound having a plurality of substituents at the meso position is generated as a by-product.

The method for producing a porphyrin-based compound having a substituent at the meso position according to the present invention comprises the step of oxidizing the porphyrinogen derivative to produce a porphyrin-based compound. It is characterized by the presence of alcohol that can be converted into (except formaldehyde).
The alcohol is not particularly limited as long as it can be converted into the aldehyde by oxidation, and a primary alcohol represented by the following general formula (V) can be used.

In the formula, R ² is not particularly limited as long as it is a monovalent organic group as described above for Q ^{1 ′ to} Q ^{8 ′} , but preferably a hydrogen atom, a halogen atom, a nitro group, a nitroso group, or a cyano group. , Isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide group, alkyl group, aryl group, or haloalkyl group Linear, branched or cyclic alkyl group which may be substituted; hydrogen atom, halogen atom, nitro group, nitroso group, cyano group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto Group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide A linear, branched or cyclic alkenyl group which may be substituted with an alkyl group, an aryl group or a haloalkyl group; a hydrogen atom, a halogen atom, a nitro group, a nitroso group, a cyano group, an isocyano group or a cyanato group , Isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide group, alkyl group, aryl group, or haloalkyl group An aryl group is mentioned. More preferably, it is substituted with a hydrogen atom, halogen atom, cyano group, isocyano group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, halogenated acyl group, alkyl group, aryl group, or haloalkyl group. Linear or branched alkyl group having 1 to 13 carbon atoms; hydrogen atom, halogen atom, cyano group, isocyano group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide group , An aryl group that may be substituted with an alkyl group, an aryl group, or a haloalkyl group.

  Although content of alcohol does not have limitation in particular, 1 mol or more is preferable with respect to 1 mol of porphyrinogen derivatives. Moreover, 4000 mol or less is preferable, More preferably, it is 3000 mol or less. When the amount is less than 1 mol, the yield of the porphyrin compound having one substituent at the meso position is deteriorated. When the amount is more than 4000 mol, a porphyrin compound having a plurality of substituents at the meso position is generated as a by-product.

  As described above, the aldehyde and / or alcohol may be present in the pre-oxidation reaction solution and / or the oxidation reaction system by adding aldehyde and / or alcohol, or pyrrole, which is the previous stage of the raw material 2-hydroxymethylpyrrole derivative. As a carboxylic acid ester derivative, a method of using an ester of a primary alcohol other than a methyl ester, or a weak acid other than a methyl ester of a weak acid and an ester of a primary alcohol to inactivate an excess reducing agent after completion of the reduction reaction. Can be used.

  Further, chloroform containing ethanol as a stabilizer as a reaction solvent, or an aldehyde (except formaldehyde) and / or an alcohol that can be converted into an aldehyde (but excluding formaldehyde) by oxidation during the reaction. Reagents, intermediates, and solvents that may generate s may be used. Preferably, the aldehyde and / or alcohol is added to the pre-oxidation reaction solution and / or the oxidation reaction system.

In oxidizing a porphyrinogen derivative, chloranil or dichlorodicyanobenzoquinone, which is usually used to oxidize a saturated hydrocarbon ring or an unsaturated hydrocarbon ring to an aromatic ring such as a benzene ring or a naphthalene ring, according to a known method. Injecting an organic oxidizing agent such as N-2,4,6-trinitrophenyl-N ′, N′-diphenylhydrazine, an inorganic oxidizing agent such as manganese dioxide and selenium dioxide, and an oxidizing gas such as oxygen Can also be used. Of these, chloranil and dichlorodicyanobenzoquinone are preferable.

The amount of the oxidizing agent is preferably adjusted by adding the oxidizing agent while monitoring the progress of the reaction by liquid chromatography or the like, but 0.3 times equivalent to 3 times the 2-hydroxymethylpyrrole derivative used as a raw material. Use equivalent weight. Preferably it is 0.3 times equivalent-1 time equivalent.
The oxidation reaction is usually carried out at room temperature, but it is also possible to carry out the reaction at a high or low temperature in order to control the side reaction rate. The desired reaction temperature is from −20 ° C. to the reflux temperature of the solvent.
When it is lower than 20 ° C., the reaction does not proceed, and the amount of porphyrin-based compound having a substituent at the meso position is reduced. Here, in order to selectively obtain a porphyrin compound having one substituent at the meso position, the reaction temperature is preferably 80 ° C. or lower.

The reaction time required for the oxidation may be determined while monitoring the progress of the reaction, but is usually 30 minutes or longer. If the oxidation reaction is carried out for too long, the yield may decrease due to side reactions. Therefore, it is desirable to adjust the amount of the oxidizing agent and the reaction temperature so that the reaction is completed within 12 hours.
The obtained porphyrin-based compound having a substituent at the meso position can be purified as necessary. As a specific purification method, the target product is taken out by concentrating the reaction solvent or adding a poor solvent. In order to further increase the purity, it can be purified to a desired purity using chromatography, recrystallization, reprecipitation or the like.

(Porphyrin compounds having a substituent at the meso position)
The porphyrin-based compound having 1 to 4 and preferably 1 substituent at the meso position of the present invention produced by the method as described above, and the compound having 1 substituent at the meso position is represented by the following general formula ( IV).

Wherein Q ¹ to Q ⁸ are as defined above Q ^{1`</sup> to Q <sup>8`.} Of these, Q ^{1 to} Q ⁸ are preferably hydrogen, an optionally substituted alkyl group, or a group represented by the above general formula (II).
R ³ has the same meaning as R ¹ , preferably a hydrogen atom, a halogen atom, a nitro group, a nitroso group, a cyano group, an isocyano group, a cyanato group, an isocyanato group, a thiocyanato group, an isothiocyanato group, a mercapto group, or a hydroxy group. , An epoxy group, a formyl group, a sulfonic acid group, a carboxyl group, an acyl halide group, an alkyl group, an aryl group, or a linear, branched or cyclic alkyl group which may be substituted with a haloalkyl group; a hydrogen atom , Halogen atom, nitro group, nitroso group, cyano group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide Group, alkyl group, aryl group, or haloalkyl group Linear, branched or cyclic alkenyl groups which may be substituted; hydrogen atom, halogen atom, nitro group, nitroso group, cyano group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto And an aryl group optionally substituted with a group, a hydroxy group, an epoxy group, a formyl group, a sulfonic acid group, a carboxyl group, an acyl halide group, an alkyl group, an aryl group, or a haloalkyl group. More preferably, it is substituted with a hydrogen atom, halogen atom, cyano group, isocyano group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, halogenated acyl group, alkyl group, aryl group, or haloalkyl group. Linear or branched alkyl group having 1 to 13 carbon atoms; hydrogen atom, halogen atom, cyano group, isocyano group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide group , An aryl group that may be substituted with an alkyl group, an aryl group, or a haloalkyl group.

M represents 2 hydrogen atoms or 1 to 2 metal atoms, and the metal atoms may be bonded to other atoms or atomic groups.
Any metal atom can be used as long as it can bond to the porphyrin compound. Among these, metals having a divalent or trivalent valence are preferable. Examples of the divalent metal include a periodic table such as Fe, Co, Ni, Cu, and Zn (IUPAC Inorganic Chemical Nomenclature 1990). A metal selected from Group 8, Group 9, Group 10, Group 11 or Group 12 of (Rule). In addition, when the metal atom is trivalent or more, other atoms such as a halogen atom and an oxygen atom, or an atomic group such as an alkyl group and an alkoxy group may be bonded, for example, Fe-X, Al-X, Ti = O, Si-X ¹ X ² (where X, X ¹ and X ² represent a monovalent group such as a halogen atom, an alkyl group, or an alkoxy group). Examples thereof include KARL M.I. KADISH KEVIN M.K. By SMITH ROGER GUILARD, THE PORPHYRIN HANDBOOK VOL. 1-10, ACADEM
Known products such as those listed in IC PRESS (2000) can be used.

  Preferred examples of such porphyrin compounds include, but are not limited to, the following examples.

  When various metals are introduced into the center (N atom) of the above compound, it can be easily carried out by reacting a metal salt such as copper acetate in a mixed organic solvent such as chloroform-methanol.

A porphyrin-based compound having a substituent at the meso position can be identified by well-known analysis such as liquid chromatography, mass spectrum, NMR, and IR.
The quantification of the porphyrin-based compound having a substituent at the meso position is not particularly limited as long as it is an ordinary method, but the composition ratio can be analyzed by, for example, NMR or liquid chromatography. From the integral ratio of the peak to the corresponding proton in the NMR spectrum, a porphyrin compound having one substituent at the meso position and a porphyrin compound having no substituent at the meso position and / or a porphyrin having a plurality of substituents at the meso position The composition ratio (= molar ratio) with the system compound can be determined. Moreover, the same sample as that used for NMR measurement can be detected by UV 254 nm, which is used for general purposes, using liquid chromatography, and the peak area can be converted into a molar ratio.

The details of the mechanism for producing a porphyrin compound having a substituent at the meso position are unknown, but considering the results of the production method of the present invention, it is considered as follows, and porphyrin is exemplified as a porphyrin compound. This will be described below.
By cyclizing 2-hydroxymethylpyrrole with an acid catalyst, porphyrinogen, a tetramer of pyrrole, is produced. In the presence of acid and water, this intermediate forms methylene group at the meso position as formaldehyde. It is considered to be in an equilibrium state with the detached one. On the other hand, when a primary alcohol such as ethanol is present when oxidizing porphyrinogen and converting it to porphyrin, the alcohol is oxidized and, for example, aldehydes such as acetaldehyde are generated. It is considered that a porphyrin compound in which a group derived from the alcohol is bonded to the meso position is generated by being oxidized after being taken into the pyrrole tetramer by the above equilibrium.

(Application of porphyrin compounds having a substituent at the meso position)
The porphyrin having a substituent at the meso position can be applied to the following.
The function is expressed by binding to other functional molecules through the substituent at the meso position. For example, bonding with an electron-accepting group such as fullerene or quinone causes electron transfer between the porphyrin and the electron-accepting group due to light absorption of the porphyrin, which facilitates charge separation. And application to photocatalysts.
In addition, by introducing a chemical bond into the side chain of a polymer using a substituent at the meso position, the function and catalytic function of porphyrin can be fixed to the polymer.
Furthermore, a porphyrin compound having an unsubstituted or substituted long-chain alkyl group in the meso position is expected to show both amphipathic properties, production of a monomolecular film by the LB method, function as a surfactant, and The combination of porphyrin functions is expected. Those in which an alkyl group is substituted with a thiol group are expected to bind to the gold surface, and this can also be used for the production of a monomolecular film. Such a monomolecular film can be expected to have a photovoltaic force and a photoelectron transfer reaction.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples unless it exceeds the gist.
The porphyrinogen derivative and the porphyrin-based compound were quantified using high performance liquid chromatography manufactured by Shimadzu Corporation. The column used was CAPCELL PAK C18 manufactured by SHISEIDO FINE CHEMICALS, and a sample of chloroform was detected while flowing a mixed solvent of THF / water = 60: 40 at a flow rate of 0.6 ml / min and a pressure of 150 kgf / cm ^2. The solution was analyzed.

Example 1
Under a nitrogen atmosphere, lithium aluminum hydride (4.41 g, 116 mmol) was suspended in tetrahydrofuran (THF, 100 ml). After cooling to 0 ° C., a solution of ethyl 4,7-dihydro-4,7-ethano-2H-isoindole-1-carboxylate (6.22 g, 28.6 mmol) in THF (60 ml) was added dropwise. Thereafter, the temperature was raised to 10 ° C., and the whole was stirred for about 3 hours. The progress of the reaction was confirmed by HPLC, and the reaction solution was added to a saturated aqueous ammonium chloride solution to stop the reaction. Thereafter, extraction was performed with chloroform (manufactured by Wako Pure Chemical Industries, Ltd., using amylene as a stabilizer) (3 times 300 ml each), and the extracted chloroform solution was concentrated. Separately, chloroform solution (700 ml) of p-toluenesulfonic acid (770.2 mg, 4.47 mmol) (manufactured by Wako Pure Chemical Industries, Ltd. using amylene as a stabilizer)
Was prepared, and compressed air was bubbled for about 10 minutes while stirring. To this acidic solution, the previously concentrated solution was added dropwise at room temperature while continuing stirring and bubbling. When confirmed by LC, the peak of 4,7-dihydro-4,7-ethano-1-hydroxymethyl-2H-isoindole produced by the reduction reaction disappears, and there is a newly appearing peak. The mass spectrum of this peak Was measured, and it was confirmed that the molecular weight was 628 and it was a corresponding bicycloporphyrinogen. After stirring and bubbling were continued for about 1 hour, 10 ml of the reaction solution was separated. Benzaldehyde (19.1 mg, 0.18 mmol) was added to the 10 ml solution, and the mixture was further stirred for about 1 hour and then left overnight. Stirring was resumed the next day and the reaction was followed by HPLC. Agitation was stopped when it was determined that equilibrium was reached, and the mixture was allowed to stand for several more days. The reaction solution prepared by the above method contains 25.9-fold molar amount of benzaldehyde with respect to porphyrinogen. In such a small-scale reaction, the reaction proceeds sufficiently only by oxidation with only oxygen in the air, and porphyrinogen is converted into porphyrin. The reaction solution was analyzed by LCMS. Bicycloporphyrin (molecular weight 622, λmax = 380 nm), monophenyl compound having one phenyl group at the meso position (molecular weight 698, λmax = 390 nm), two phenyl groups at the meso position A peak for the diphenyl compound (molecular weight 774, λmax = 398 nm) was confirmed. Assuming that the molar absorbance system number of each peak is equal, the production ratio was determined from the ratio of the area at each λmax. Bicycloporphyrin: monophenyl form: diphenyl form = 87.0: 10.7: 2.3.

(Example 2)
Under a nitrogen atmosphere, lithium aluminum hydride (2.6621 g, 70.1 mmol) was suspended in tetrahydrofuran (THF, 100 ml). Cool to 0 ° C. (cooling bath temperature) and ethyl 4,7-dihydro-4,7-ethano-2H-isoindole-1-carboxylate (3.9277 g, 18.4 mmol) in THF (140 ml) The solution was added dropwise (the temperature of the internal reaction solution rose from 6 ° C. before the addition to 8.5 ° C. after the addition). Thereafter, the temperature was raised to 10 ° C., and the whole was stirred for about 3 hours. The progress of the reaction was confirmed by HPLC, and the reaction was stopped by adding ethyl acetate (17.6 ml). The reaction solution was added to a saturated aqueous ammonium chloride solution, followed by extraction with chloroform (2 × 500 ml). The extracted chloroform solution was concentrated to about 70 ml. This solution was added dropwise to a chloroform suspension (700 ml) of p-toluenesulfonic acid (552.0 mg, 2.82 mmol) at room temperature. The chloroform used here contains a maximum of 7 ml (124 mmol) of ethanol as a stabilizer. The mixture was stirred for about 1 hour and left overnight. Stirring was resumed the next day and chloranil (1.1290 g, 4.6 mmol) was added at room temperature. When the progress of the reaction was confirmed by HPLC, porphyrinogen as a reaction intermediate remained, and chloranil (570.9 mg, 2.3 mmol) was further added at room temperature. After confirming disappearance of porphyrinogen by HPLC, the reaction solution was poured into water to stop the reaction, and the organic layer was separated. Since the above ethanol is oxidized by chloranil to acetaldehyde, it is taken into porphyrinogen by an acid-catalyzed exchange reaction. This introduces a methyl group at the meso position when porphyrin is produced by oxidation of porphyrinogen. The extract was washed with an aqueous sodium hydrogen carbonate solution (twice) and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the target product was separated by silica gel column chromatography (developing solvent was chloroform) and purified by reprecipitation using a chloroform-methanol solvent to obtain a meso-position-free porphyrin and a meso-position methyl-substituted porphyrin derivative. (1.1150 g in total, 40.0% (unsubstituted 33.6%, methyl-substituted 6.0%).

Claims (5)

A method for producing a porphyrin-based compound having a substituent at a meso position, comprising a step of oxidizing a porphyrinogen derivative represented by the following general formula (I) in which two hydrogen atoms are bonded to all four meso positions Because
When oxidizing the porphyrinogen derivative, an aldehyde represented by the following general formula (IV) (however, excluding formaldehyde) is present in the system.
A method for producing a porphyrin-based compound having a substituent R ³ at the meso position.

(Wherein, Q ¹ 'to Q ^8' indicates a monovalent group independently selected from the following group, of which, (Q ^{1 'and Q 2'), (Q 3} ' and Q ^{4 '} ), (Q ^5' and Q ^{6 '} ), and (Q ^7' and Q ^{8 '} ) may be bonded to each other to form a ring structure.
In the following groups , Q ⁹ is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, and Q ¹⁰ and Q ¹¹ are each independently a hydrogen atom, a hydroxyl group , a hydrocarbon group, a heterocyclic group, an acyl group represented by -COQ ^9, a carboxylic acid ester group or a sulfonyl group represented by -SO ₂ Q ⁹ represented by -COOQ ^9, Q ¹² and Q ¹³ Are each independently a hydrogen atom, a hydrocarbon group or a heterocyclic group. )
Group : hydrogen atom; fluorine atom; chlorine atom; bromine atom; nitro group; nitroso group; cyano group; isocyano group; cyanato group; isocyanato group; thiocyanato group; isothiocyanato group; mercapto group; hydroxy group; A sulfonic acid group; a carboxyl group; an optionally substituted alkyl group; an optionally substituted cycloalkyl group; an optionally substituted alkenyl group; an optionally substituted cycloalkenyl group; A good aryl group; an optionally substituted heterocyclic group; an optionally substituted alkoxy group; an optionally substituted alkenyloxy group; an optionally substituted aryloxy group; an optionally substituted alkylthio acyloxy group represented by -OCOQ ^9;; acyl group represented by -COQ ^9; group -NQ ¹ Sulfinyl group represented by -SOQ ^9;; The carbamoyl group represented by -CONQ ¹² Q ^13; carboxylic acid ester group represented by -COOQ ^{9; 0} amino group represented by Q ¹¹ in -SO ₂ Q ⁹ A sulfonyl group represented; a sulfonate group represented by —SO ₃ Q ⁹ ; a sulfamoyl group represented by —SO ₂ NQ ¹² Q ¹³

(In the formula, R ¹ represents a monovalent organic group selected from organic groups groups below.)
Organic group: hydrogen atom, halogen atom, nitro group, nitroso group, cyano group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfonic acid group, A linear, branched or cyclic alkyl group which may be substituted with a carboxyl group, an acyl halide group, an alkyl group, an aryl group, or a haloalkyl group; a hydrogen atom, a halogen atom, a nitro group, a nitroso group, a cyano group Group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide group, alkyl group, aryl group, or haloalkyl group Linear or branched chain optionally substituted by Or cyclic alkenyl group; hydrogen atom, halogen atom, nitro group, nitroso group, cyano group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfone group, a carboxyl group, an acyl halide group, an alkyl group, a substituted group R ³ aryl groups, or haloalkyl optionally substituted by an aryl group (a porphyrin-based compound having a substituent group R ³ in the meso-position, the A monovalent organic group selected from the organic group group exemplified by R ¹ is shown .) ” When oxidizing the porphyrinogen derivative, an alcohol represented by the following general formula (V), which can be converted to the aldehyde (except formaldehyde) by oxidation, is present in the system. Item 2. A method for producing a porphyrin-based compound having a substituent at the meso position according to Item 1.

(Wherein, R ² is Ru monovalent organic group Der selected from organic Group below.)
Organic group: hydrogen atom, halogen atom, nitro group, nitroso group, cyano group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfonic acid group, A linear, branched or cyclic alkyl group which may be substituted with a carboxyl group, an acyl halide group, an alkyl group, an aryl group, or a haloalkyl group; a hydrogen atom, a halogen atom, a nitro group, a nitroso group, a cyano group Group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfonic acid group, carboxyl group, acyl halide group, alkyl group, aryl group, or haloalkyl group Linear or branched chain optionally substituted by Or cyclic alkenyl group; hydrogen atom, halogen atom, nitro group, nitroso group, cyano group, isocyano group, cyanato group, isocyanato group, thiocyanato group, isothiocyanato group, mercapto group, hydroxy group, epoxy group, formyl group, sulfone An aryl group optionally substituted with an acid group, a carboxyl group, an acyl halide group, an alkyl group, an aryl group, or a haloalkyl group) 3. The meso of claim 1 or 2, wherein the porphyrinogen derivative is synthesized by acid treatment of a 2-hydroxymethylpyrrole derivative represented by the following general formula (III '). Of a porphyrin-based compound having a substituent at the position.

(In the formula, R represents a group corresponding to Q ^{1 ′ to} Q ^{8 ′} of the general formula (I).) The method for producing a porphyrin-based compound having a substituent at the meso position according to any one of claims 1 to 3, wherein the substituent has two substituents at the meso position. The method for producing a porphyrin-based compound having a substituent at the meso position according to any one of claims 1 to 3, wherein the substituent has one substituent at the meso position.