JPH0354670B2 - - Google Patents

Description

[Detailed Description of the Invention] The present invention relates to the general formula (where n is an integer of 1 to 20 and X is a halogen atom)
The present invention relates to a 10,15,20-tetra[α,α,α,α-o-(substituted amido)phenyl]porphine complex. Many reports have been made of iron-porphine complexes that can form oxygen complexes in organic solvents at room temperature. Examples include J.P.Collman, Accouhts of
Chemical Research, 10 , 265 (1977) or F.
Basolo, B. M., Hoffman and JAIbers,
ibid., 8 , 384 (1975). etc. However, these iron-porphine complexes have the disadvantage that they are immediately oxidized when even a small amount of water is present, and cannot produce oxygen complexes. Moreover, these complexes also have the problem of not being soluble in water. It has been reported that a very stable oxygen complex can be formed in anhydrous aprotic solvents, especially under room temperature conditions. (pivalamide) phenyl]
Porphin complexes (JP Collman et al., Journal of
the American Chemioal Society, 97, 1427
(1975)) is immediately oxidized as it is when it comes into contact with water, but by embedding it in a liposome membrane formed from an appropriate phospholipid, it can reversibly adsorb and desorb oxygen in water at room temperature. It is possible to obtain a liposome-dispersed aqueous solution of a porphin complex.
E. Hasegawa et al., Biochemical and Bjophyaical
Research Communicatics, 105 , 1416 (1982).
was reported. The purpose of the present invention is to make a poorly soluble iron-tetraphenylporphine derivative water-soluble while retaining its oxygen adsorption/desorption function, or to make it possible to make a slightly soluble iron-tetraphenylporphin derivative water-soluble while retaining its oxygen adsorption/desorption function, or to use a small amount of surfactant, phospholipid, synthetic water-soluble polymer, polysaccharide, The object of the present invention is to provide a novel iron-tetraphenylporphine complex having a hydroxyl group necessary for improving the ability to be easily and uniformly dissolved in an aqueous solution containing water-soluble proteins. Although the compound of the general formula obtained by the present invention is itself insoluble in water,
General formula easily obtained by chemically modifying the hydroxyl group
(where n is an integer of 1 to 20) It is an important synthetic intermediate of an iron-tetraphenylporphine complex having a phosphorylcholine group. The compound of the general formula forms an oxygen complex in a homogeneous aqueous solution at room temperature in the presence of a suitable basic ligand, preferably a substituted imidazole ligand, with the central iron in a divalent state, and reversibly absorbs oxygen. It is a very useful oxygen adsorbing/desorbing agent or oxygen carrier because it can be desorbed. For the above reasons, the novel iron tetraphenylporphine complex having a hydroxyl group represented by the general formula of the present invention has value as an important synthetic intermediate. According to the invention, novel complexes of the formula (where n is an integer from 1 to 20) and J.P. Collman et al., Journal of the
American Chemical Society, 97 , 1427 (1975)
The expression reported in 5, 10, 15, 20-tetra (α, α,
α,α-o-aminophenyl)porphin (hereinafter referred to as
Abbreviated as H ₂ TamPP. ) in the presence of a base, the obtained formula is (where n is the same as defined above), the benzyl group was removed with anhydrous aluminum chloride in the presence of anisole, and the resulting formula
(where n is as defined above) is reacted with ferrous bromide in the presence of pyridine, and a suitable mineral acid such as 48% hydrobromic acid, concentrated hydrochloric acid, iodide By treatment with hydrogen acid or the like, a novel complex represented by a desired general formula in which bromide ions, chloride ions, or iodine ions are coordinated can be synthesized. Furthermore, a compound of the general formula that can be used as a useful oxygen adsorbing/desorbing agent can be obtained by reacting the compound of this general formula with 2-chloro-2-oxo-1,3,2-dioxaphosphorane to form a phosphoric acid enteryl compound. It can be easily synthesized by further reacting with excess trimethylamine, and the general formula serves as an important synthetic intermediate. The starting material for the general formula is a new compound, which was synthesized by the following method. ω-benzyloxyalkyl halide by George R. Newkome et al., Synthesis,
The dilithium anion of 2-methylpropionic acid produced according to the report of 1975, 517.
I reacted with The reaction mixture is then decomposed with cold dilute hydrochloric acid and the solvent extracted crude product is recrystallized in a non-polar solvent such as petroleum ether, n-hexane, n-heptane and ω-benzyloxy-2,2- Dimethylalkanoic acid was obtained as colorless crystals. This is reacted with an excess amount of thionyl chloride in a nonpolar solvent, preferably benzene or carbon tetrachloride, or without a solvent, and then concentrated under reduced pressure to produce ω-benzyloxy-2,2-dimethylalkanoic acid represented by the general formula Obtained chloride. raw material formula (Here, n has the same meaning as defined earlier,
X' represents chlorine or bromine. ). ω
-benzyloxyalkyl halide, n=1,
When X=Cl, AJHill et al., Journal of the
American Chemical Society, 48 , 257, (1926)
According to the report of S., when n=2 and X'=Br.
Cremer et al., Journal of the American
It can be synthesized according to the report of Chemical Society, 86 , 4197 (1964). Further, when n=3 to 20 and X'=Br, it can be obtained by refluxing α,ω-dibromoalkane with 1 equivalent of sodium benzyl oxide in benzene. An excess amount of the carboxylic acid chloride of the general formula is mixed with a known substance, H ₂ TamPP, in an anhydrous aprotic solvent, preferably tetrahydrofuran, dichloromethane,
Residue obtained by reacting in chloroform, N,N-dimethylformamide or acetone solution in the presence of excess triethylamine or pyridine at 0°C to room temperature, pouring into water and extracting with chloroform, and evaporating the separated extract. A compound represented by the general formula can be obtained by purifying it by silica gel column chromatography. In order to remove the benzyl group of the benzyl ether represented by this general formula, dichloromethane:
The mixture was reacted with excess anhydrous aluminum chloride in a mixed solvent of nitromethane in the presence of an excess amount of anisole at -5°C to 30°C, preferably 15°C to 25°C for 2 to 12 hours. The reaction mixture was poured into ice water, extracted with chloroform, the extract was washed with water, and then
After washing with a % sodium bicarbonate aqueous solution, the separated chloroform layer was dried with sodium sulfate, and the residue obtained by evaporating the chloroform was recrystallized from benzene or a mixed solvent of dichloromethane-benzene. To introduce iron into the resulting compound of general formula, J.P. Collman et al., Journal of the American
The reaction was carried out with excess ferrous bromide in the presence of pyridine in anhydrous tetrahydrofuran at reflux under a nitrogen atmosphere, following the method reported in Chemical Society, 97 , 1427 (1975). Purification by column chromatography using alumina or silica gel, and treatment of the resulting eluate with hydrochloric acid, hydrobromic acid, or hydroiodic acid, results in the formation of chlorine, bromine, or iodine as a counter ion, and the central iron is
A compound of the desired general formula is obtained in a valent state. The introduction of a phosphorylcholine group into this important synthetic intermediate was carried out by NSChandrakumar et al.
It is made according to the report of Tetrahedron Letters, 23 , 1043 (1982), and the compound of the general formula can be easily synthesized. A compound of the general formula is prepared in an anhydrous aprotic solvent such as dichloromethane, chloroform or benzene in the presence of pyridine in an amount of 1 to 2 equivalents based on the alcohol group.
1 to 2 equivalents of 1,3,2-dioxaphosphorane were added dropwise at 0°C to room temperature, followed by reaction at room temperature for 6 to 24 hours. The reaction solution was distilled off under reduced pressure, and the resulting residue was evaporated into acetonitrile or N,N-
Dissolve in dimethylformamide, add trimethylamine, and incubate at 50° or more in a stainless steel sealed tube container.
The reaction was carried out at 65°C for 12 to 24 hours. The reaction mixture was filtered to obtain a brown precipitate. After washing this with acetone, methanol or water is added using an appropriate gel such as Cephadex G-25, Cephadex LH-60 (manufactured by Pharmacia), or Toyopearl HW-40 (manufactured by Toyo Soda Co., Ltd.). A compound of the desired general formula can be obtained by column chromatography using a solvent. This complex is transferred to an aqueous medium (e.g. water, buffer solution (PH4).
pH 10 to 10), physiological saline, etc.), and a basic ligand, preferably a substituted imidazole ligand, is dissolved in
A 1 to 1000 times equivalent amount, preferably a 5 to 200 times equivalent amount was added, and nitrogen was bubbled to form a deoxygenated aqueous solution. To reduce the central iron from trivalent to divalent, 1
A method of adding 1 to 10 times the amount of sodium dithionite, sodium borohydride, or ascorbic acid, a method of reduction with hydrogen gas in the presence of a palladium black or palladium carbon catalyst, E.
Hasegawa et al., Biochemical and Biophysical
Research Communications, 104 , 793 (1982)
The enzyme-based reduction method reported in 2010 can be used. The aqueous solution of the iron() complex obtained by reduction becomes an oxygen complex when oxygen is blown into it at room temperature, and returns to the original iron() complex when nitrogen is blown into it, confirming reversible adsorption and desorption of oxygen. As described above, the novel iron-tetraphenylporphine complex having a hydroxyl group represented by the general formula of the present invention has significance as an important synthetic intermediate for the compound having the general formula which acts as a useful oxygen adsorbent. The present invention will be explained in more detail by the following examples, which are not intended to limit the invention. Reference example 1 10-benzyloxydecanyl bromide is 1,
100 g of 10-dibromodecane and an equivalent amount of sodium benzyl oxide were refluxed in tetrahydrofuran, and the precipitate was filtered, concentrated, and then distilled under reduced pressure. yield
46g, boiling point 185-189℃/3mmHg. George R. Newkome et al., Synthesis, 1975,
517, with lithium diisopropylamide in tetrafuran under nitrogen atmosphere.
- Lithium dianion of methylpropionic acid was generated, 18 g of 10-benzyloxydecanyl bromide was added dropwise at -20°C, and the mixture was reacted at 45°C for 2 hours.
The reaction mixture was added to cold diluted hydrochloric acid and extracted with ether, and the separated ether layer was washed with diluted hydrochloric acid and then with water, separated and dried over Glauber's salt. The crude oil obtained by evaporation to dryness was recrystallized from petroleum ether to obtain 8.4 g of colorless crystals of 12-benzyloxy-2,2-dimethyldodecanoic acid in a yield of 46%. melting point 53
~55℃. Elemental analysis: Calculated value (%) as C ₂₁ H ₃₄ O ₃ ; C75.40, H10.25, Analysis value (%); C75.64,
H10.09. Proton nuclear magnetic resonance spectrum ( _CDCl3 ) δppm: 1.18 (6H, s, _-CH3 ), 1.26
(16H, s, -CH ₂ -), 3.46 (2H, t, PhCH ₂ CH
₂ CH ₂ −), 4.51 (2H, s, Ph CH ₂ O−), 7.33
(5H, s, phenyl proton). Dissolve 3.34 g of this obtained carboxylic acid in 5 ml of anhydrous benzene, add 1.2 ml of thionyl chloride, and stir at room temperature for 12 hours.
After reacting for an hour and drying under reduced pressure, a colorless oil of 12-
Benzyloxy-2,2-dimethyldodecanoic acid chloride was obtained in a yield of 3.53 g. Infrared absorption spectrum (CCl ₄ ) ν1790cm ^-1 ([Formula]). Proton nuclear magnetic resonance spectrum ( _CDCl3 )
δppm: 1.28 (22H, s, _-CH3 and _-CH2- ),
3.46 (2H, t, _{PhCH2OCH2CH2-} ) _{, 4.50}
(2H, s, _PhCH2O- ), 7.32 (5H, s, phenyl proton). Example 1 5,10,15,20-tetra (α, α, α, α-o
-aminophenyl) porphin (hereinafter H ₂ TamPP
It is abbreviated as ) is J.P.Collman et al., Journal of
American Chemical Society, 97 , 1427 (1975)
Synthesized according to the literature. A solution of 1.0 g of H ₂ TamPP in anhydrous tetrahydrofuran (40 ml) was added with 0.81 ml of pyridine, and 3.53 g of 12-benzyloxy-2,2-dimethyldodecanoic acid chloride obtained in Reference Example 1 was added dropwise at room temperature, and the mixture was allowed to react for 3 hours. Ta. After extraction with ether and washing with water, the separated ether layer was dried with Glauber's salt and dried under reduced pressure. The crude product obtained was purified by silica gel column chromatography using a mixed solvent of benzene and ether (volume ratio 15:1) to give a brown color. 5,10,15,20-tetra[α,α,α,α-o-(12-benzyloxy-
1.69 g of 2,2-dimethyldodecanamido)phenyl]porphine was obtained in a yield of 60%. Infrared absorption spectrum (CHCl ₃ ) ν3440, 3330,
3000, 2930, 2860, 1680, 1580, 1510, 1450,
1300, 1100, 970, ^{910, 700cm -1} . Proton nuclear magnetic resonance spectrum ( _CDCl3 )
δppm: −2.6 (2H, s, N H in the porphine ring),
−0.23 (24H, s, −C(CH ₃ ) ₂ CONH−), 3.46
(8H, t, PhCH ₂ OCH ₂ CH ₂ −), 4.50 (8H,
s, Ph CH ₂ O-), 7.12 (4H, s,
[Formula]), 7.32 (20H, s), 8.82 (8H, s). Example 2 5,10,15,20-tetra [α, α, α, α-o
-(12-benzyloxy-2,2-dimethyldodecanamido)phenyl] 1.68 g of porphine was dissolved in a mixed solvent of 25 ml of anhydrous dichloromethane and 25 ml of nitromethane, 2 ml of anisole was added, and then 2 g of anhydrous aluminum chloride was added and kept at room temperature for 4 hours. Made it react. The mixture was poured into 100 ml of ice water to decompose excess aluminum chloride, extracted with dichloromethane, and the separated dichloromethane layer was washed with water and then with a 10% aqueous sodium bicarbonate solution, separated, dried over sodium sulfate, and concentrated under reduced pressure. . The residue was recrystallized from benzene to give purple plate-like crystals of 5,10,15,20-tetra[α,α,α,α-o-(12-hydroxy-2,2
-dimethyldodecaneamide) phenylporphine was obtained in a yield of 1.10 g, with a yield of 80%. Melting point 127-129.5
℃. Magnetic field desorption mass spectrum: 1579 (M+1) ⁺ infrared absorption spectrum (KBr) ν3600-3350 (wide range), 3440, 3330, 2940, 2860, 1690, 1585,
1515, 1450, 1302, 1060, 970, 810, 770, 740cm
^-1 . Proton nuclear magnetic resonance spectrum ( _CDCl3 )
δppm: −2.59 (2H, s, pyrrole NH ), −0.22
(24H, s, -C(C H ₃ ) ₂ -CONH-), 3.64
(8H, t, HOC H ₂ CH ₂ −), 7.15 (4H, s),
7.36-8.73 (16H, m) 8.82 (8H, s). In addition, 4.50 (8H, s) and 7.32 derived from benzyl group
The absorption of (20H, s) disappeared. Elemental analysis: Calculated value (%) as C ₁₀₀ H ₁₃₈ N ₈ O ₈ ;
C76.00, H8.00, N7.09: Analysis value (%);
C75.62, H8.90, N709. Example 3 5,10,15,20-tetra [α, α, α, α-o
-(12-Hydroxy-2,2-dimethyldodecanamido)phenyl] 0.65 g of porphine was dissolved in anhydrous tetrahydrofuran (50 ml), and 0.3 g of pyridine was dissolved.
ml and after purging with nitrogen, 2.0 g of ferrous bromide tetrahydrate was added and refluxed under nitrogen for 3 hours.
After extraction with chloroform and washing with water, the separated chloroform layer was dried with Glauber's salt and the solvent was distilled off under reduced pressure. The resulting residue was purified by alumina column chromatography using a mixed solvent of chloroform/methanol (volume ratio 9/1). . Add the elution solution to 2 ml of 48% hydrobromic acid.
After stirring, drying with Glauber's salt and evaporating to dryness, a black-purple solid of bromo{5,10,15,20-tetra[α,α,
0.38 g of α,α-o-(12-hydroxy-2,2-dimethyldodecanamido)phenyl polyfinato}iron () was obtained in a yield of 54%. Melting point 76~
79℃. Magnetic field desorption mass spectrum: 1713 (M+1) ⁺ However, the molecular formula is C ₁₀₀ H ₁₃₆ N ₈ O ₈ FeBr = 1712. Infrared absorption spectrum (KBr): ν3600~3150
(broad), 3440, 2930, 2860, 1690, 1580,
1510, 1440, 1300, 1075, 1000, 805, 760,
715 cm ^-1 . Elemental analysis: Calculated value (%) as C ₁₀₀ H ₁₃₆ N ₈ O ₈・FeBr; C70.13, H8.00, N6.54, analytical value (%);
C70.37, H8.40, N6.63. Reference Example 2 Phosphorylcholine of the tetraalcohol obtained in Example 3 was described by NSChandrakumar et al.
It can be carried out as reported in Tetrahedron Letters, 23 , 1043 (1982). Bromo {5, 10, 15, 20−
Tetra [α, α, α, α-o-(12-hydroxy-2,2-dimethyldodecanamide) phenyl]
A solution of 0.15 g of iron () in anhydrous dichloromethane (10 ml) and 0.07 ml of triethylamine
and 0.08 g of 2-chloro-2-oxo-1,3,2-dioxaphosphorane were added and reacted at room temperature for 12 hours. The reaction was completed using silica gel thin layer chromatography (solvent chloroform/methanol = 10/
1) causes the spot with Rf value 0.30 to disappear and Rf value 0.40
This can be confirmed from the generation of spots. The solvent was distilled off under reduced pressure, the residue was dissolved in 25 ml of anhydrous acetonitrile, and 5 ml of trimethylamine was added at -60 to -40°C, the mixture was sealed in a pressure-resistant stainless steel container, heated to 60 to 65°C, and reacted for 16 hours. The black precipitate obtained by cooling to room temperature was dissolved in methanol and purified by gel column using Sephadex LH-60, and the eluted solution was evaporated to dryness and then vacuum-dried in the presence of phosphorus pentoxide. Iron ()-5, 10, 15, 20 as a black solid
-tetra {α, α, α, α-o-[12-(2′-trimethylaminoethyl)phosphoryloxy-2,2
-dimethyldodecaneamide]phenyl}porphine complex was obtained in an amount of 0.18 g, with a yield of 90%. Infrared absorption spectrum (KBr): ν3650~3150
(broad), 3430, 2940, 2860, 1690, 1580,
1510, 1440, 1220, 1080, 1000, 950, 800,
760, 710 cm ^-1 . Visible absorption spectrum (H ₂ O): λ _nax 412, 564 nm. Reference example 3 1,18-dibromooctadecane is, for example, Lester
Friedman and Arnon Shani, Journal of the
American Chemical Society, 96 , 7101–7103.
(1974). In the same manner as in Reference Example 1, 18.3 g (yield: 41%) of 18-benzyloxyoctatecanyl bromide was obtained from 42 g of 1,18-dibromooctadecane instead of 1,10-dibromodecane. 18 g of this was reacted with lithium dianion (equivalent mole) of 2-methylpropionic acid, and after the same extraction treatment as in Reference Example 1, the crude oil obtained was converted into a mixed solution of benzene:ether (volume ratio 15:
1) was purified by silica gel column chromatography to obtain colorless crystals of 20-benzyloxy-
2,2-dimethyleicosanoic acid was obtained in a yield of 5.7 g and a yield of 31%. Melting point 72-73℃. Elemental analysis: Calculated value (%) as C ₂₉ H ₅₀ O ₃ ; C,
77.97, H, 11.28, analysis value (%); C78.25,
H11.21. Infrared absorption spectrum (KBr) ν: 2930, 2860,
1705, 1470, 1130, 1120, 950, 740, 700cm ^-1 . Proton nuclear magnetic resonance spectrum ( _CDCl3 )
δppm: (6H, s, -C( _CH3 ) _2COOH ), 1.25
(32H, brsPhCH ₂ OCH ₂ (CH ₂ ) ₁₆ CH ₂ −), 3.46
(2H, t, J=6.5Hz, PhCH ₂ OCH ₂ CH ₂ −),
4.50 (2H, s, PhC _H2O- ), 7.33 (5H, m, benzene ring proton). 5.2 g of this obtained carboxylic acid was reacted with 4 ml of thionyl chloride at room temperature for 4 hours and dried under reduced pressure to obtain 5.6 g of colorless solid 20-benzyloxy-2,2-dimethyleicosanoic acid chloride. Infrared absorption spectrum ( _CCl4 ) ν: 2930, 2860,
1790, 1460, 1365, 1100, 905, ^{700cm -1} . Example 4 5.6 g of the obtained 20-benzyloxy-2,2-dimethyleicosanoic acid chloride was mixed with 1.3 g of H ₂ TamPP.
of anhydrous tetrahydrofuran (50 ml) and pyridine (1.5 ml) under the same conditions as in Example 1.
After post-treatment and purification, 5,10,15,20-tetra[α,
α,α,α-o-(20-benzyloxy-2,2
-dimethyl-eicosanamido)phenyl]porphin was obtained in an amount of 3.70 g, with a yield of 80%. Melting point 33~
35℃. Elemental analysis: Calculated value (%) as C ₁₆₀ H ₂₃₀ N ₈ N ₈ ;
C80.29, H9.68, N4.68, analysis value (%);
C80.11, H9.88, N4.77. Infrared absorption spectrum (KBr) ν: 3440, 2920,
2850, 1690, 1580, 1510, 1450, 1360, 1300,
1100, 965, 800, 750 cm ^-1 . Proton nuclear magnetic resonance spectrum ( _CDCl3 )
δppm: -2.60 (2H, s, N- in the porphine ring
H), −0.22(24H, s, −C(CH ₃ ) ₂ −CONH
−), 3.45 (8H, t, J=6.4Hz, PhCH ₂ OC H ₂
CH ₂ −), 4.49 (8H, s, PhC H ₂ O), 7.13 (4H,
s, [formula]), 7.31 (20H, s, [formula]), 8.76 (4H, d, J=7Hz,
[Formula]), 8.82 (8H, s, porphine ring β-position proton) Example 4 5,10,15,20-tetra [α, α, α, α-o
-(20-benzyloxy-2,2-dimethyleicosanamido)phenyl] 3.5 g of porphine was added to dichloromethane (30 ml) in the same manner as in Example 2.
After reaction with 6 g of anhydrous aluminum chloride in a mixed solvent of nitromethane (15 ml) and anisole (3 ml), the residue was subjected to post-treatment and extraction, and dried under reduced pressure. 1) and refine it,
It was recrystallized from a mixed solvent of dichloromethane and methanol. Reddish brown needle crystals of 5,10,15,20-tetra[α,α,α,α-o-(20-bitroxy-2,
1.89 g of 2-dimethyleicosanamido)phenyl]porphine was obtained in a yield of 64%. Melting point 88~
90℃ Infrared absorption spectrum (KBr) ν: 3430, 3320,
2920, 2860, 1675, 1580, 1510, 1470, 1450,
1300, 970, 805, 760, 720 cm ^-1 Proton Nuclear Magnetic Resonance Spectrum (CDCl ₃ )
δppm: -2.60 (2H, s, N- in the porphine ring
H), −0.21(24H, s, −C(CH ₃ ) ₂ −CONH
−), 3.69 (8H, t, J=6.4Hz, HOC H ₂ CH ₂
−, 7.14 (4H, s, amide group −CON H −),
8.73 (4H, d, J=7Hz,
[Formula]), 8.82 (2H, s, proton at β position of porphyrin ring). Elemental analysis: Calculated value as C ₁₃₂ H ₂₀₂ N ₈ O ₈ (%);
C78.14, H9.98, N5.52, analysis value (%);
C78.42, H10.20, N5.39. Example 5 5,10,15,20-tetra [α, α, α, α-o
-(20-hydroxy-2,2-dimethyleicosanamido)phenyl] 1.06 g of porphine was reacted in the same manner as in Example 3, followed by silica gel column chromatography (mixed solvent of chloroform/methanol = 15/1). ) and further recrystallized from a mixed solvent of dichloromethane/methanol. Black-purple crystals of bromo{5,10,15,20-tetra[α,α,α,α-o-(20-hydroxy-
2,2-dimethyleicosanamido)phenyl]
Porphynato} Iron () yield: 0.82g, yield 73%
I got it from Melting point 49-50℃. Infrared spectrum (KBr) ν: 3430, 2930,
2860, 1690, 1580, 1510, 1460, 1440, 1300,
1000, 800, 760 ^{, 720cm -1} . Elemental analysis: C ₁₃₂ H ₂₀₀ N ₈ O ₈ FeBr: Calculated value (%) as 1/2 CH ₂ Cl; C72.16, H9.19, N5.08, Analysis value (%); C72.41, H9.09 , N4.92. Reference example 4 Bromo {5, 10, 15, 20-tetra [α, α,
0.55 g of α,α-o-(20-hydroxy-2,2-dimethyleicosanamido)phenyl]porphynate iron (2-chloro-2-oxo- After reacting with 0.30 g of 1,3,2-dioxaphosphorane, the residue was dried under reduced pressure and dissolved in a mixed solvent of N,N-dimethylformamide (15 ml) and acetonitrile (15 ml).
After adding 10 ml and reacting, after similar post-treatment and purification, iron()-5,10,15,20- was obtained as a black solid.
Tetra {α, α, α, α-o-[20-(2′-trimethylaminoethyl)phosphoryloxy-2,2-
A dimethyleicosanamide]phenyl}porphine complex was obtained in an amount of 0.45 g with a yield of 61%. melting point 235
~237℃ Infrared absorption spectrum (KBr) ν: 3430 (wide range),
2940, 2860, 1690, 1590, 1515, 1470, 1440,
1300, 1230, 1090, 1000, 970, 810, 760, 730
cm ^-1 . Elemental analysis: Calculated value (%) as C ₁₅₂ H ₂₄₈ N ₁₂ O ₂₀ P ₄ Fe・9H ₂ O; C62.83, H9.23, N5.78, Analysis value (%); C62.55, H9.42 , N5.99. Reference example 5 Benzyloxymethyl chloride is described by AJHill et al.
Journal of the American Chemical Society,
48, 257 (1926), and this
10.96g was converted into an equivalent amount of 2
-Methylpropionic acid was reacted with lithium dianion and purified by recrystallization from n-hexane to obtain 7.75 g of 3-benzyloxy-2,2-dimethylpropionic acid in a yield of 53%. Melting point 72-74℃. Infrared absorption spectrum (KBr) ν: 3400~2400
(broad) 1700, 1480, 1320, 1250, 1120,
940, 740, 700cm−1. Proton nuclear magnetic resonance spectrum ( _CDCl3 )
δppm: 1.23 (6H, s, _-CH2C ( _CH3 ) _2COOH ),
3.47 (2H, s _{, PhCH2OCH2C} ( _CH3 ) _2- ),
4.55 (2H, s, PhC _H2O- ), 7.31 (5H, s, phenyl ring proton). Elemental analysis: Calculated value as C ₁₂ H ₁₆ O ₃ (%);
C69.20, H7.75, analysis value (%); C69.43,
H7.80. Add 3.0 g of the obtained carboxylic acid to 4 ml of thionyl chloride.
was reacted in the same manner as in Reference Example 1 to quantitatively obtain 3-benzyloxy-2,2-dimethylpropionic acid chloride as an oil. Infrared absorption spectrum ( _CCl4 ) ν: 1830, 1790,
1460, 1100, 915 ^{, 700cm -1} . Example 6 3.4 g of 3-benzyloxy-2,2-dimethylpropionic acid chloride was added in the same manner as in Example 1.
After reacting with 1.1 g of H ₂ TamPP, it was purified by silica gel column chromatography using chloroform/ether = 15/1 as a solvent, and recrystallized from a dichloromethane-methanol mixed solvent.
5, 10, 15, 20-tetra [α, α, α, α-o-
Yield: 1.92 g of (3-benzyloxy-2,2-dimethylpropanamido)phenyl]porphin.
Obtained with a yield of 82%. Melting point 170-172℃ Infrared absorption spectrum (KBr) ν: 3440, 3320,
2970, 2860, 1690, 1605, 1583, 1510, 1450,
1310, 1155, 1095, 1080, 970, 800, 755,
740, 700cm ^-1 proton nuclear magnetic resonance spectrum ( _CDCl3 )
δppm: −2.53 (2H, s, N in the porphine ring
H), 0.05 (24H, s, -C( _CH3 ) ₂ -CONH-),
2.72 (8H, s, _PhCH2OCH2- ), _3.29 (8H,
s, PhCH ₂ COH ₂ −) 6.46-6.56 (8H, m,
[Formula]), 6.88-6.96 (12H, m, [Formula]), 8.70 (8H, s, proton at β-position of porphine ring), 8.15 (4H, s,
[Formula]) 8.80 (4H, d, J=7.3 Hz, [Formula]), 7.33-7.90 (12H, m, [Formula]). Elemental analysis: Calculated value (%) as C ₉₂ H ₉₀ N ₈ O ₈ ;
C76.96, H7.81, analysis value (%); C76.81, H6,
41, N7.72. Example 7 5,10,15,20-tetra[α,α,α,α-o-(3-benzyloxy-2,2-dimethylpropanamido)phenyl] was prepared in the same manner as in Example 2.
1.5 g of porphine was subjected to a debenzylation reaction and recrystallized from benzene to obtain 5,10,15,20-tetra[α,α,α,α-o-(3-hydroxy-2,
1.09 g of 2-dimethyl-propanamido)phenyl]porphine was obtained in a yield of 96%. Melting point 294
~297℃ Infrared absorption spectrum (KBr) ν: 3430 (broad),
3280 (broad), 1760, 1615, 1590, 1530,
1470, 1450, 1350, 1310, 1290, 1160, 1050,
970, 820, 810, 760 cm ^-1 . Proton nuclear magnetic resonance spectrum ( _CDCl3 )
δppm: −2.89 (2H, brs, porphin ring N
H), -0.78 (2H, brs, hydrated _H2O ), 0.49 (24H,
s, -C( _CH3 ) _2CONH- ), 1.02(4H, brt, H
OCH ₂ −), 2.22 (8H, d, J=4Hz, HOC H ₂
C( _CH3 ) _2- ), 7.35(4H,s,-C( _CH3 ) _2- )
CON H −), 8.85 (8H, s, porphine ring β-
position proton). Elemental analysis: Calculated value (%) as C ₆₄ H ₆₆ N ₈ O ₈・H ₂ O; C70.31, H6.27, N10.24, analytical value (%); C70.60, H6.34, N9. 97. Example 8 5, 10, 15, 20-
Tetra [α, α, α, α-o-(3-hydroxy-2,2-dimethylpropanamidonophenyl)]
0.89 g of porphine was reacted with ferrous bromide, tetrahydrate, purified with a mixed solvent of chloroform/methanol = 15/1, and recrystallized from benzene/methanol to obtain bromo{5,10,15,20- Tetra [α,
0.37 g of α,α,α-o-(3-hydroxy-2,2-dimethylpropanamido)phenyl]porphynato}iron () was obtained in a yield of 38%. Melting point over 300℃. Infrared absorption spectrum (KBr) ν: 3420 (broad),
3250 (broad), 1670, 1610, 1585, 1525,
1440, 1330, ₁₀₅₀ , 1000, 800, ₇₆₀ , 720 cm ^-1 Elemental analysis: Calculated value (%) as C ₆₄ H ₆₄ N 8 O 8 FeBr・H ₂ O; C62.65, H5.42, N9.13, Analysis value (%);
C62.36, H5.46, N9.01.

Claims (1)

[Claims] 1 formula (where n is an integer of 1 to 20 and X is a halogen atom) iron-5,10,
15,20-tetra[α,α,α,α-o-(substituted amidophenyl]porphine complex.