Process for the production of metalloporphyrin-metal complex...

Details Process for the production of metalloporphyrin-metal complex... Process for the production of metalloporphyrin-metal complex...

1999-09-21

2001-02-27

Shah, Mukund J. (Department: 1624)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C424S001650, C424S001850, C424S009610, C534S014000, C534S015000

Reexamination Certificate

active

06194566

ABSTRACT:

The invention relates to the subject that is characterized in the claims, i.e., a process for the production of metalloporphyrin-metal complex conjugates that contain at least one ion of an element of atomic numbers 20-32, 37-39, 42-51 or 57-83 in the complex part of the conjugate. Up until now, metalloporphyrin-metal complex conjugates were produced according to multistage processes. In EP 0 336 879, tetraphenylporphyrins are first reacted with a complexing agent, then with a metal oxide or metal salt for complexing the complexing agent and then with manganese acetate for substitution of the pyrrolic NH groups. The reaction with manganese acetate is carried out at 80° C. in glacial acetic acid. The use of the acetate has the drawback that it is not possible to work either with excesses or under anhydrous conditions. The usability of this process is therefore limited.
From EP 0 355 041 is known a process for the production of metalloporphyrin-metal complex conjugates, in which first the manganese is inserted into the porphyrin core, and then the reaction is carried out with a complexing agent and a metal oxide or metal salt for complexing the complexing agent. This procedure has a decisive drawback. The immobilization on the metal in the porphyrin is carried out as early as in the first stage, so that for a variation of the porphyrin metal in the case of uniform complexing agents, the synthesis for each new porphyrin metal must be performed each time for at least three stages. In this case, it is not possible to avoid drawbacks such as, e.g., losses in yield and effects in the area of environmental protection, such as, e.g., an increase in the amount of metal-containing wastes.
The object of this invention was therefore to provide a synthesis method for metalloporphyrin-metal complex conjugates, which does not exhibit the above-mentioned drawbacks, but mainly makes possible a more economical synthesis scheme in the case of variation of the porphyrin metal and the presence of sensitive groups.
This object is achieved by the process according to the invention, as it is characterized in the claims.
This is a process for the production of metalloporphyrin-metal complex conjugates, which is characterized in that a porphyrin-metal complex conjugate is converted into a metalloporphyrin-metal complex conjugate by reaction with a metal acetylacetonate in a protic or aprotic polar solvent or solvent mixture at temperatures from room temperature to 150° C. at concentrations of 3-30%.
The insertion-of the central metal atom into the porphyrin core is carried out by a recomplexing reaction with metal acetylacetonate, i.e., the metal that is already bonded in a complex manner in the acetylacetonate makes a switch from its complex ligand acetylacetone to complex ligand porphyrin and is also bonded in a complex manner by the latter.
A special embodiment of the invention is a process for the production of metalloporphyrin-metal complex conjugates of general formula I
that contain at least one ion of an element of atomic numbers 20-32, 37-39, 42-51 or 57-83 in the complex part of the molecule, in which
M stands for an ion of metals magnesium, aluminum, chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium, technetium, indium, tin, europium, lutetium, thallium, bismuth or oxovanadium(IV),
R
1
stands for a hydrogen atom, for a straight-chain C
1
-C
6
alkyl radical, a C
7
-C
12
aralkyl radical or for a group OR′,
whereby R′ is a hydrogen atom or a C
1
-C
3
alkyl radical,
R
2
stands for R
3
, a group —CO—Z or a group —(NH)
o
—(A)
q
—NH—D,
whereby Z is a group —OL, with L in the meaning of an inorganic or organic cation or a C
1
-C
4
alkyl radical,
A means a phenylenoxy group or a C
1
-C
12
alkylene or C
7
-C
12
aralkylene group that is interrupted by one or more oxygen atoms,
o and q, independently of one another, mean the numbers 0 or 1,
D means a hydrogen atom or a group —CO—A—(COOL)
o
—(H)
m
, with m equal to 0 or 1 and provided that the sum of m and o is equal to 1,
R
3
stands for a group —(C═Q)(NR
4
)
o
—(A)
q
—(NR
5
)—K,
whereby Q stands for an oxygen atom or for two hydrogen atoms,
R
4
means an —(A)
q
—H group, and
K means a complexing agent of general formula (IIa), (IIb), (IIc), (IId) or (IIe), and
R
5
, if K is a complexing agent of Formula (IIa), has the same meaning as R
4
, and if K is a complexing agent of Formula (IIb), (IIc), (IId) or (IIe),
R
5
has the same meaning as D, provided that a direct oxygen-nitrogen bond is not allowed
and K stands for a complexing agent of general formulas (IIa), (IIb), (IIc), (IId) or (IIe)
 in which
o and q have the above-indicated meanings,
A
1
has the meaning that is indicated for A,
R
6
stands for a hydrogen atom, a straight-chain or branched C
1
-C
7
alkyl group, a phenyl or benzyl group,
A
2
stands for a phenylene group, a —CH
2
—NHCO—CH
2
—CH(CH
2
COOH)—C
6
H
4
—&bgr; group, a phenylenoxy group or a C
1
-C
12
alkylene or C
7
-C
12
aralkylene group that is optionally interrupted by one or more oxygen atoms, 1 to 3 —NHCO and/or 1-3 CONH groups and/or substituted with 1 to 3 —(CH
2
)
0-5
COOH groups,
 whereby &bgr; stands for the binding site to X,
X stands for a —CO— or NHCS group, and
L
1
, L
2
, L
3
, and L
4
, independently of one another, stand for a metal ion equivalent of an element of the above-mentioned atomic numbers, provided that at least two of these substituents stand for a metal ion equivalent, and other anions are present to compensate for optionally present charges in the metalloporphyrin-metal complex conjugate and in which free carboxylic acid groups that are not required for complexing can also be present as salts with physiologically
compatible inorganic and/or organic cations or as esters or as amides,
characterized in that
porphyrin-metal complex conjugates of general formula (III)
 in which R
1
, R
2
, R
3
and R
4
have the above-indicated meanings, are converted into metalloporphyrin-metal complex conjugates of Formula (I) by reaction with a metal acetylacetonate of metal M in a protic or aprotic polar solvent or solvent mixture at temperatures from room temperature to 150° C. in concentrations of 3-30%.
As metal M, the metals magnesium, aluminum, chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium, technetium, indium, tin, europium, lutetium, thallium, bismuth and oxovanadium(IV) are suitable. Preferred are magnesium, aluminum, chromium, manganese, iron, cobalt, nickel, copper, zinc, tin, lutetium and oxovanadium(IV). Especially preferred are manganese, iron, copper and zinc.
The metals are present in porphyrin, if not otherwise indicated, as divalent or trivalent ions. If an ion that is bonded in the porphyrin is present in a higher oxidation stage than +2, the excess charge(s) are compensated for by, e.g., anions of organic or inorganic acids, preferably by acetate, tartrate, succinate, maleate, chloride, sulfate and nitrate ions or by negative charges that are present in R
2
and/or R
3
.
Preferred alkyl radicals R
1
are straight-chain C
1
-C
3
alkyl radicals. Especially preferred is the methyl radical.
Alkyl radical R′ can be a methyl, ethyl, propyl or isopropyl radical.
Aralkyl radicals R
1
can be benzyl or 4-methoxybenzyl.
Inorganic cations L are, for example, the lithium ion and the potassium ion, especially the sodium ion.
Organic cations L are, for example, cations of organic bases; cations of primary, secondary or tertiary amines, such as, for example, ethanolamine, diethanolamine, morpholine, glucamine, N,N-dimethylglucamine, especially meglumine, can be mentioned.
Alkyl radical Z can be straight-chain or branched. Methyl and ethyl are preferred.
R
2
and R
3
preferably stand for the same radical. R
2
and R
3
preferably stand for groups —CONHNH—K, —CONH—(CH
2
)
2
—NH—K, —CONH—(CH
2
)
3
—NH—K, —CONH—(CH
2
)
4
—NH—K and —CONH—(CH
2
)
2
—O—(CH
2
)
2
—NH—K. Especially preferred is the group —CONHNH—K.
The meaning of an oxygen atom is preferred for Q.
R
4
is preferably hydrogen.
Preferred complexing agents K are complexing

Affiliated with

Also associated with

Rating

Process for the production of metalloporphyrin-metal complex... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for the production of metalloporphyrin-metal complex..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the production of metalloporphyrin-metal complex... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2584612