CA2187949A1 - Electron-deficient porphyrins and processes and intermediates for preparing same - Google Patents

Electron-deficient porphyrins and processes and intermediates for preparing same

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Publication number
CA2187949A1
CA2187949A1 CA002187949A CA2187949A CA2187949A1 CA 2187949 A1 CA2187949 A1 CA 2187949A1 CA 002187949 A CA002187949 A CA 002187949A CA 2187949 A CA2187949 A CA 2187949A CA 2187949 A1 CA2187949 A1 CA 2187949A1
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CA
Canada
Prior art keywords
carbon atoms
acid
electron
formula
group
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
CA002187949A
Other languages
French (fr)
Inventor
Michael J. Therien
Stephen Dimagno
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University of Pennsylvania Penn
Original Assignee
Individual
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Filing date
Publication date
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Publication of CA2187949A1 publication Critical patent/CA2187949A1/en
Abandoned legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A—HUMAN NECESSITIES
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    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/545—Heterocyclic compounds
    • A61K47/546—Porphyrines; Porphyrine with an expanded ring system, e.g. texaphyrine
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
    • A61K51/0485—Porphyrins, texaphyrins wherein the nitrogen atoms forming the central ring system complex the radioactive metal
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/48—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by oxidation reactions with formation of hydroxy groups
    • C07C29/50—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by oxidation reactions with formation of hydroxy groups with molecular oxygen only
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • C07—ORGANIC CHEMISTRY
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    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
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    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/90—Catalytic systems characterized by the solvent or solvent system used
    • B01J2531/92—Supercritical solvents
    • B01J2531/922—Carbon dioxide (scCO2)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/90—Catalytic systems characterized by the solvent or solvent system used
    • B01J2531/96—Water

Abstract

Electron-deficient porphyrins are provided, as well as processes and intermediates for their preparation. In preferred embodiments, the electron-deficient porphyrins are prepared by condensing pyrrole derivatives and removing water thus formed from the resulting reaction mixture.

Description

~ 1 879/'~9 wo 9~29916 1 ~""~ - I
.

~r.~c~rRn~_DEFICIENT PO~,~YK.Lhi~ AND
PROCESSES AND ~ r~c FOR PREPARING SAME
FIELD OF THE lNVI~
This invention relates to porphyrins bearing electron-withdrawing substituents such as perhaloalkyl groups, and to techniques and int.o -~;~t~.: useful in preparing such rr,mr~ nr~.
13ACKGROUN~ OF THE lNV~ ~ L1~N
Porphyrins are derivatives of porphine, a conjugated cyclic structure of four pyrrole rings linked through their 2- and 5-positions by met_ine bridges. Porphyrins can be covalently attached to other molecules. The electronic features of the porphyrin ring system can be altered by the att~chm~nt of one or more substituents. The term "porphyrin~
includes derivatives wherein a metal atom is inserted into the ring system, as well as molecular systems in which ligands are attached to the metal. The substituents, as well as the overall porphyrin structure, can be neutral, positively charged, or negatively charged.
Electron-deficient porphyrins (i . e., porphyrins bearing substituents that are electron-withdrawing relative to hydrogen) have been sugge8ted f or use as industrial oxidation catalysts. A number such compounds have been prepared, typically through rrn~l~nf:~tion of suitably substituted aldehydes and/or pyrroles. Xowever, known 8ynthetic methods generally proceed in low yield, if at all, and cannot be used to produce many types of electron-deficient porphyrins. Accordingly, there exists a need in the art for W0 95/29916 r~
.

efficient synthetic methods caFable of producing a greater variety of such c~ In~
OBJECTS OF T~lE lN V~l~ _ It is one object of the present invention to provide 5 improved methods for synthesizing electron-deficient porphyrins .
It is another object of the invention to provide novel electron-deficient porphyrins.
It is yet another object to proYide novel compounds 10 that include electron-deficient porphyrins.
It is yet another object to provide synthetic precursors of electron-deficient porphyrins.
It is a further obj ect of the invention to provide polymers cnnt:?;n;n~ linked electron-deficient porphyrins.
1~ It is still another object to provide new applications for electron-deficient porphyrins and compounds that contain them.
S~MMARY OF TIIE lN V ~ lUN
These and other objects are satisfied by the present 20 invention, which provides novel electron-deficient porphyrins and methods for their preparation. In preferred embodiments, the electron-deficient porphyrins have formula (1), ~2~, or (3):
R~RB R~RB
R A~ ~H ~R ~ R I~ /U\ ~R A
RB r --RB RB J ~RB
RB RA RB RB RA RB
(1) (2) WO 95129916 2 ~ 8 7 9 4 ~ P~

R ~ R~
~N~ N~
R A~/ ~,~, ~R A
R B r R
RB RA R~
~3) wherein M and M' are metal atoms and at least one of RA is a group that is electron-withdrawing relative to ~ydLO~eLl. In pre~erred embodiments, at least one R.A is a perhaloalkyl group or a perhaloaryl groups and at least one RB group is H, 5 perhaloalkyl, perhaloaryl, NOz, F, Cl, Br, or CN.
In accordance with the invention, these and other electron-deficient porphyrins are prepared by first preparing an electron-deficient porphyrinogen, a partially-oxidized, electron-deficient porphyrinogen, an electron-deficient 10 polypyrryl intermediate, or a partially-~ l;z~l, electron-deficient polypyrryl intermediate (together, porphyrinogens and polypyrryl intermediates) through pyrrole-based condensation reactions wherein at least a portion of the generated water in such reactions is removed from the reaction 15 mixture. In certain embodiments, porphyrinogens and polypyrryl intermediates are prepared by condensing an aldehyde having formula R"-CHO with a pyrrole derivative having formula (4) (q = 0, 1, or 2~ . Alternatively, such compounds are prepared by condensing hydroxymethylpyrrole 20 h ing formula (5) (n = 0, 1, or 2).

WO 95/29916 r~

R ~ B R ~ B R ~ ~ B
H--~N~C--~N~--H H--~N~N~--C-OH
H RA_ q H _ H RA_ n H RA
(4) (5) Porphyrinogens and polypyrryl intP ~ tes also can be prepared by condensing bis-hydroxymethylpyrrole having formula (6) (n = O, 1, or 2) with a pyrrole having formula (7).
HO-C--~C--~C-OH R~B
RA _ H RA_ n H R~ H
(6) (7) Porphyrinogens and~ polypyrryl intermed1ates thus formed can 5 be directly oxidized or can be isolated and then oxidized.
Oxidation of porphyrinogens yields porphyrins and/or partially oxidized porphyrinogens. Oxidation of polypyrryl intermediates yields partiaIly-oxidized polypyrryl intermediates that can be further condensed and/or oxidized 10 to form porphyrins, porphyrinogens, and/or further polypyrryl intermediates .
In another aspect, the invention provides polymers comprising linked porphyrin units, at least one of such units being an electron-APfi~ nt porphyrin. In certain 15 embodiments, porphyrin units having formula 11), ~2), or (3) share covalent bonds. In other embodiments, at least one RA
group or RB group functions as a linking group. In these f.mho~ -ntS, at least a portion of a linking group can have formula [C (RC) =C (RD) (RE) ] X~ [C-C (RD) ] X~ [CH2 (RC) ~CH (RD) (RE) ] X or 20 [CH=CX(RD)]x where RC~ RD' and RE are, independently, H, F, C1, Br, I, alkyl or heteroalkyl having from 1 to about 20 carbon atoms, aryl or heteroaryl having about 4 to about 2 0 carbon atoms, alkenyl or heteroalkenyl having f rom 1 to about 2 0 .. . . .. .. . _ . _, . _ _ .. . _ .. ~ . .. . .... . .

095129916 2 1 ~ 9 4 q .
s carbon atoms, alkynyl or heteroalkynyl having $rom 1 to about 20 carbon atomE, trialkylsilyl or porphyrinato, provided that at least one of RC~ RD~ and RE is not H and x is at least 1.
RC, RD~ and RE al80 can include peptides, nucleosides, and/or 5 saccharides. The rr~~inin~ of R" and R8 can be H, halogen, alkyl or heteroalkyl having 1 to about 20 carbon atoms or aryl or heteroaryl having 4 to about 20 carbon atoms, C(RC)=C(RD) (R), C}C(RD), or a chemical functional group that includes a peptide, nucleoside, and/or saccharide. In other 10 preferred embodiments, the linking group is cycloalkyl or aryl having about 6 to about 22 carbon atoms.
The invention al80 provides processes for preparing porphyrin-containing polymers. In certain embodiments, the processes comprise providing at least two compounds that, 15 ;nri~r~n(l~ntly, have formula (1), (2), or (3) wherein at least one RA group or RB group in each of the compounds c~nt~in~ an olef inic carbon- carbon double bond or a chemical f unctional group reactive therewith. In other embodiments, at least one R~ group or RB group in each of the compounds c~nt~;n~ a 20 carbon-carbon triple bond or a chemical functional group reactive therewith. The compounds are then contacted for a time and under reaction conditions effective to form covalent bonds through the carbon- carbon double and/or triple bonds .
The porphyrins and porphyrin-containing polymers of 25 the invention can be used, for example, as dyes, catalysts, contrast agents, antitumor agents, antiviral agents, and in chemical sensors and electrooptical devices.
nr~TA Tr.~!n DESCRIPTION OF T~IE INVENTION
It has been found in accordance with the present 30 invention that a wide variety of novel porphyrins can be prepared by ~-nnr~n~At;on of suitably functionalized pyrroles provided that at least a portion of the water of cr~n~n~tion is removed from the reaction mixture. In general, the resulting porphyrins have formula (1), (2), or (3):

WO 9~/29916 2 1 8 7 9 4 9 1 ~
R ' ~ _ ~, R ~ ~ R B
R B~ ~; ~ ; ~ / R B
RB RA RB RB RA RB
(1) (2) R~ ,~ RB
~ `11 ' ~R I
R a~I ~~ R B
RB RA RB
(3) wherein M and M' are metal atoms, at least one RA is a group that i8 electron-withdrawing relative to hydrogen, and at least one RB is H or an acid-stable chemical functional group.
M preferably is a lanthanide or actinide or a- metal 5 such as Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Y, Zr, Nb, Mo, Ru, Rh, Pd, Ag, La, Hf, Ta, W, Re, Os, Ir, Pt, Cd, Hg, Li or Au.
More preferably, M is Cr, Mn, Fe, Co, Ni, Ru, Rh, Pd, Os, Ir, Pt, or Au. M' can be a metal such as Li, ~a, K, Rb, or Cs, preferably Li.
At least one RA in the compounds of the invention is an alkyl group that is electron-withdrawing relative to hydrogen . The rr-- n n~ RA and R} groups can be the same or different and are selected from H and those groups known to be stable under the acidic reaction conditions of the 15 invention, including alkyl, alkenyl, alkynyl, and aryl groups.
(see, e.g., Application Serial No. 08/064,468) In preferred ~ W095129916 2 1 ~ 1 9~q l~l/L~ _.
embodiments, the RA groups are selected such that they are not each pF~rh~ 1~ ;1 l kyl having 1 to 4 carbon atoms, phenyl, dihalophenyl, perhalophenyl, or CN, and the R3 groups are selected such that they are not perfluoromethyl, NOz, CN, or 5 halogen. Those skilled in the art will recognize that chemical protecting groups can be attached to acid-sensitive functionality found within RA and/or R~ and can be removed after cnn~F~ncation has been completed. (see, e.g., Greene and Wuts in Protective Groups in Organic Synthesi~, John Wiley &
10 Sons, Inc., 1991~ .
Compounds having formulas (1) - (3) preferably bear 1, 2, 4, 8, or 12 substituents (i.e., 1, 2, 4, 8, or 12 of RA
and R!3 are not H). In certain c~ , four RA groups bear electron-withdrawing functionality.
Numerous examples of electron-withdrawing functional groups are known to those skilled in the art. Further, electron-withdrawing groups can be identified through routine experimentation involving, for example, replacement of hydrogen in a molecule with a given group and then testing any 20 resultant inductive effects. Representative electron withdrawing groups include the following: N- (alkyl) 3~, NH3~, NO2, SO2-(alkyl), CN, SO2-(aryl), C(O)OH, F, Cl, Br, I, C(O)O-talkyl), C (O) - (alkyl), and/or CHO, wherei~ alkyl groups have from about 1-30 carbon atoms and aryl groups have about 3-50 25 carbon atoms. In preferred embodiments, alkyl and aryl groups have from 1 to about 20 carbon atoms and about 6 to about 20 carbon atoms, respectively. More preferably, alkyl groups have from 5 to about 20 carbon atoms and aryl groups have from about 6 to about 20 carbon atoms. The terms alkyl and aryl 30 are ;nt~nrll~fl to include moieties substituted with, for example, halogens or nitro groups, as well as moieties wherein heteroatoms (e.g., N, O, S, Se, and Te) are inserted into the carbon ba-k~nnP of an alkyl or aryl structure to yield, for example, an ether, thioether, and pyridinyl group. Alkyl and 35 aryl groups can bear substituents that include additional carbon atoms. Preferred electron-withdrawing groups are substituted and unsubstituted alkyl and aryl groups that ., .. . .. . .. .. . .. _ .. _ .. _ .. .. .. .. . , .. _ _ _ _ _ _ _ _ 6 2 ~ 87~49 pos3ess net electron-withdrawing effects. P~r~ r~lkyl ana perhaloaryl groups are particularly preferred, including perf luoroalkyl, perf luorophenyl, perf luorobenzyl, and tetraf luoropyridyl groups .
In certain Pr.~Q~; ' c, porphyring according to the invention are prepared by synthesizing and then oxidizing 3uitably-substituted porphyrinogen ~ ~ ~u1.ds having, for example, f ormul as ( 8 ) and ( 9 ) .
R B ~ R R R E-- ~ ~' r ?-- R B
R A~N N R A~ H j A
R B~/~R 3 R B~J~R B

(8) (9) In other embodiments porphyrins are prepared by rrn~ n~tion lO and oxidation of suitably-substituted polypyrryl intermediates having, fpr- exampl~e, formulas (lO) and (ll) .
R~ RE R~ ~B R~ ~E
R Z--~--C~--C~N~--C - O
H RA H RA H RA
(10) R ~ 3 R ~ 5 B R ~ E
R Z--~N ~--ClN~--C--~ N ~--C - O H
H RA RA H RA
(11) 21 8794~
wo 951~9916 , ~
Porphyrinogens and polypyrryl intermediates can be prepared by condensing aldehydes having formula R,~-CHO with pyrroles derivative having formula (4) (q = 0, l, or 2).
Alternatively, such cn~r-mln~c are prepared by cnn~l~n~; n~
5 alcohols having formula (5) (n = 0, l, or 2).
R~J9 R~ R~B R~B
H--~N~C--~N~--H H ~ ~N~ C_OH
H RA_ q H N R~ n H R~
(4) (5) Porphyrinogens and polypyrryl intermediates also can be prepared by condensing alcohols having formula (6) (n = 0, l, or 2) with pyrroles having formula (7).
HO-C ~C ~C-OH R~B
RA _ H A_ n H RA H
(7) (6) 0 Each of these reactions should be performed in organic solvent in the presence of acid for a time and under conditions effective to form a reaction mixture comprising water and an adduct of the reagents. In accordance with the invention, at least a portion of the water thus formed is removed from the 15 reaction mixture.
A wide variety of organic solvents can be used in the synthetic processes of the invention, including benzene, toluene, xylenes, methylene chloride, chloroform, trichloroethylene, and mixtures thereof . Aprotic solvents are 20 preferred, particularly nonpolar, aprotic solvents. Solvents capable of f orming azeotropes ( i . e ., constant boiling mixtures) with water are particularly preferred.
Acids according to the invention are ions or molecules having the capacity to accept at least one electron WO95/29916 ~ f 8 7 9 ~q , ~", pair. Representative acid~ clude benzoic acid, sulfonic acid3 (e.g., p-toluenesulfonic acid and methanesulfonic acid), trifluoracetic acid, boron trifluoride, boron trichloride, and mixtures thereof. Preferred acids are not volatile under 5 reactions conditio~s of the invention. Protic acids, particularly strong protic acids (i.e., those having pK, ~ O), are preferred. In preferred embodiments, a catalytic (i . e., non-stoichiometric) amount of acid is used.
Water can be removed from adduct-rr~n~in;nr~ reaction 10 mixtures by a wide variety of known techniques, including membrane-based separations. Water also can be removed by contacting a reaction mixture with moieties that absorb, trap, or react with water or otherwise render water non-reactive.
In general, the chosen technique should remove at least a 15 portion of any water present but should not remove the adduct-forming reagentE. Representative water removal techniques are disclosed by U.S. Patent No. 4,332,643 (Reid), European Patent Application EP 92-114390 (Inaba, et al . ), Japanese Patent Applications 91-146674 ~Miyazaki, et al . ), 91-20083 (Kondo, 20 et al.), and 90-104128 (Okazaki, et al.), and Brazilian Patent Application 77-433 (Scaglia, et al . ) . Water preferably is removed by distilling an azeotrope formed by the water and the organic solvent. In certain e~r~odiments, the distilled azeotrope is collected in a vessel and allowed to separate 25 into aqueous and organic phases, and the organic (solvent) phase is returned to the reaction mixture. In other embodiments, the distilled azeotrope is contacted with a drying agent and the dried distillate is returned to the reaction mixture. Representative drying agents include 30 phosphorous pentoxide, calcium hydride, calcium oxide, barium oxide, lithium aluminum hydride, molecular sieves, and mixtures thereof. Numerous additional drying agents are well-known to persons of ordinary skill in the art. In further rl;r- t c, the dried distillate is collected and a roughly 35 esIual volume of fresh solvent is added to the reaction mixture. In still further embodiments, semi-permeable Wo 9S129916 membrane technology is used to remove water from the reaction mixture as it is formed.
Hydroxymethylpyrroles having formulas (5) and (6) preferably prepared by contacting a pyrrole having formula (7) with base in organic solvent in the presence of an aldehyde having formula RA-CHO. Representative bases include sodium hydroxide, lithium hydroxide, potassium hydroxide, barium hydroxide, alkyl or aryl lithium reagents, and alkyl or aryl Grignard reagents, with sodium hydroxide being preferred. The pyrrole, aldehyde, and base can be reacted simultaneously or in a number of different ways. For example, the pyrrole can be contacted with base and then added to the aldehyde, or can be contacted with base in the presence of aldehyde. In certain ~ tfi, pyrrole, aldehyde, and base are contacted in the absence of solvent.
Oxidation of porphyrinogens and polypyrryl intermediates can be accomplished by a number of techniques.
For example, porphyrinogen- and/or polypyrryl-containing reaction mixtures can be exposed to oxidizing conditions.
Alternatively, such .~ ~ In~lc are isolated from a reaction mixture and then contacted with an oxidizing agent.
Representative oxidizing agents include oxygen, p-chloranil, 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ~, and mixtures.
oxidation of electron-deficient compounds also can be effected using bulk electrochemical methods (see, e.g., ~aboroatory Techniques in Electroanalytical Chemistry, P.T. ICissinger and W.R. TTP;n , eds., New York, Marcel Dekker, 1984) . In general, oxidation conditions for partially-oxidized porphyrinogens and polypyrryl ;ntf~ tes (e.g., formulas (9) and (11) ) will be less vigorous than for porphyrinogens and polypyrryl intermediates in more reduced form (e.g., formulas (8) and (10) ) . More electron-deficient porphyrinogens generally require more vigorous oxidation conditions .
The processes of the invention produce somewhat n( ic compounds that can be incorporated into porphyrin-containing homopolymers or copolymers or into macromolecular wo 95129916 --l2 A .~
or supramolecular species rnnt~;n;n~, for example, one or more peptides, nucleosides, or saccharides. Polymers according to the invention can contain as few as 2 porphyrin units, but more preferably contain at least 3 porphyrin units, more 5 preferably at least 5 porphyrin units. In certain embodiments, polymers of the invention comprise a plurality of porphyrin units that, independently, have formula (l), (2), or ( 3 ) wherein at least one RA group or RB group includes a linking group selected from [c(Rc)=c(RD) (RB)]X' [C~C(RD)]X~
10 [C~2 (RC) ~CH (RD) (RB) ] X or [CH=CH (RD) ] X where x is at least The rr---; n; ng RA and RB include at least one group that is electron-withdrawing relative to l1yd. o~
In other embodiments, polymers according to the invention comprise a plurality of porphyrin units that, 15 independently, have formula (l), (2), or (3) wherein at least one RA group or RB group is a cycloalkyl, cycloalkenyl, aryl or heteroaryl linking group having about 6 to about 22 carbon atoms .
Those skilled in the art will recognize tke wide 20 variety of polymers that can be prepared from the porphyrin-cnnt~;n;ng compounds of the invention. In certain ~mho~; ts, rnf~r;~l polymers are formed having, for example, formula (12). (see, e.g., Durand, et al., J. Am. Chem. Soc., 1983, 105, 2710).
R~
R
(12) In other ' -';~~ ~, somewhat linear polymer chains are formed wherein a portion of the polymer has general formula (PN) ~ where PN is a porphyrin unit and r is at least 21 8794~
Wo 95129916 2. In ~urther emboditnents, linear polymer chains have general f ormula:
[ (QL) 1 (PN) ] h - where QL is a linking group, PN is a porphyrin unit, and h, l, 5 and s are independently selected to be at least l. For example, a portion of such polymers can have formula:
[ (PN1) ~ (QL1) 1' (PN2) ~ (QL2) 1'' ] 1 wherein PN1 and PN2 are independently selected porphyrin units, QL1 and QL2 are independently selected linking groups, and l', lO l' ', s', and 5' ' are at least l. These essentially linear polymer chains can be cross-linked such that a portion of the polymer has general f ormula:
[ (QU) h (PN) U ] V
wherein QN is a linking group, and h, u, and v are 15 independently selected to be at least l. A portion of these cross-linked polymers can have formula:
[ (PN3) U~ (QH1) h' (PN1) U (QH2) h' ] ~
wherein PN3 is a porphyrin unit, QH1 and Q82 are independently selected linking groups, and h~, h~ ', u', and u' ' are at least 20 l. Thus, cross-linked polymers can have formulas:
[ (QL) 1' (PN) ~ ] h' ( N) r' QH
PN
PN
(PN) r [ (QL) 1 (PN) ~ ] h where r~ is at least l.
The polymers of the invention can be formed by contacting a substituted porphyrin with a second compound c~ nt~;n;nr, functionality that i5 reactive with the fl~nrt;nni~l;ty cr~nt~;n~fl within the porphyrin. Preferably, the porphyrin rnntiq;nc an olefinic carbon-carbon double bond, a carbon-car~on triple bond or some other reactive functionality. The contacting should be performed under conditions effective to form a covalent bond between the respective reactive functionalities. Preferably, porphyrin-rnnt~ln;n~ polymers are formed by metal-mediated cross-W095~9916 ~ ~ 8 7949 1 1 --coupling of, for example, di~L~ n~ted porphyrin units. Al30, porphyrin-c~ntA;n;n~ polymers can be synthesized using known terminal alkyne coupling chemistry. (see, e.g., Patai, et al., The Chemistry of Flln~ n~l Groups, Supplement C, Part 1, pp.
5 529-534, Wiley, 1983; Cadiot, et al., Acetylenes, pp. 597-647, Marcel Dekker, 1964; and E~1; ntnn, et al ., Adv. Org. Chem., 1963, 4, 225) As will be recognized, the second compound noted above can be a substituted porphyrin of the invention or some other moiety such as an acrylate monomer. Thus, a 10 wide variety of copolymeric structures can be synthesized with the porphyrins of the invention. Through careful substituent selection the porphyrins of the invention can be illcorporated into virtually any polymeric matrix known in the art, including but not limited to polyacetylenes, polyacrylates, 15 polyolef ins, polyethers, polyurethanes, polycarbonates, poly:~n; 1 ;nP~, polypyrroles, and polythiophenes . For example, fluorescent porphyrins can be incorporated into such polymers as end-capping groups.
The porphyrins and porphyrin-containing polymers of 20 the invention can be used, for example, as dyes, catalysts, contrast agents, antitumor agents, antiviral agents, liquid crystals, in ~-h~m;c~l sensors and in electrooptical and solar energy conversion devices. One preferred use for compounds containing electron-deficient porphyrins are as catalysts for 25 the oxygenation ~of alkanes and/or alkenes, particularly oxygenations performed in supercritical carbon dioxide Electron-deficient porphyrins also can be incorporated into supramolecular structure~. The polymers and supramolecular structures, which anchor porphyrin units in a relatively 30 stable geometry, should improve many of the known uses for porphyrins and even provide a number of new uses, such as in a solid phase system for gterilizing virus-c~-nt;~;n;ng solutions. Representative uses are disclosed by, for example, the following patents, which are incorporated herein by 35 reiereILce: IJ.S. Patent No. 4,895,682 (Ellis, et al.); U.S.
Patent No. 4,986,256 (Cohen); U.S. Patent No. 4,668,670 (Rideout, et al.); U.S. Patent No. 3,897,255 (Erickson); U.S.

~ Wl>95129911i 2 1 8 7 9 4 9 Patent No. 3,8g9,334 (Erickson); U.S. Patent No. 3,687,863 (Wacher); U S. Patent No. 4,647,478 (Formanek, et al.); and U.S. Patent No. 4,957,615 (Ushizawa, et al.). Further uses are disclosed are disclosed by, for example, U.K. Patent 5Application 2,225,963 (Casson, et al.); TntP~n~tional Application WO 89/11277 (Dixon, et al . ); International Application WO 91/09631 (Matthews, et al. ); European Patent Application 85105490 . 8 (Weishaupt, et al. ); European Patent Application 90202953 . 7 (Terrell, et al . ); EIlL~ec..l Patent 10 Application 89304234 .1 (Matsushima, et al . ); Lehn, Angew.
Chem. Int. Ed. l~ngl., 1988, 27, 89; Wasielewski, Chem. Rev., 1992, 92, 435; Mansury, et al., J. Chem. Soc., Chem. Comm., 1985, 155; Groves, et al., J. Am. Chem. Soc., 1983, 105, 5791;
and Giroud-Godquin, et al., Angew. Chem. Int. E~d. E~ngl., 1991, 30, 375. It is believed that the porphyrins of the invention can be substituted for the porphyrins disclosed in each of the foregoing publications.
Additional objects, advantages, and novel features of this invention will become apparent to those skilled in the art upon examination of the following examples thereof, which are not intended to be limiting.
Example Preparation Of 2 - (2, 2, 3, 3, 4, 4, 4-~Iepta~luoro-1-LydL~,~yLutyl)pyrrole From ~leptafluorobutyraldehyde ~Iydrate Heptafluorobutyraldehydehydrate (9.26g, 42.9mmol) was placed in a 100 mL Schlenk flask. This was frozen with liquid nitrogen and an inert atmosphere was est~hl; ~:h~d.
Against an outflow of nitrogen, dried pyrrole (5.95 mL, 85.8 mmol) and sodium hydroxide (4.52 g, 113 mmol) were added. The flask was wrapped in foil and the mixture was stirred - overnight, during which time it solidif ied . A colorless liquid also was present. The volatiles were removed by vacuum, leaving a light brown solid. The solid was dissolved in 40 mL of water and the solution was extracted (4 x 50 mL) with methylene chloride. The organic layers were dried over sodium sulfate and then evaporated to dryness under vacuum to . . . ~

W095/29916 21 87~4q r~.,~,..;

give 5.39 g (47%) of a light yellow-brown solid. ~ NMR, (CDCl3, 360 MHz) d 8.50 ~r 1~; 6.87 m lH; 6.32 m lH; 6.22 m lH; 5.28 d, J = 8.17 Hz; 5.23 d, J = 7.67 Hz; 2.42 br 9.
Exi mple 2 5 Pr~p--ration Of 2 - (2, 2, 3, 3, 4, 4, 4-Eleptafluoro-1-L~.l u,yL-.tyl)pyrrole From Using Organolithium Re~g~nts Dry, distilled pyrrole (80 mmol) i8 dissolved in diethyl ether (200 ml) and cooled to -78C. Butyl lithium (80 mmol, 32 ml of 2.5 M solution in hexane) i8 added dropwise 10 with stirring and the solution is gradually warmed to room temperature with evolution of hydrogen. This solution is transferred dropwise by cannula to a -78C solution of dry heptafluorobutyraldehyde (previously distilled from P20s) in tetrahydrofuran (THF). The solution is warmed to room 15 temperature with stirring. The volatiles are removed by vacuum leaving a solid that is dissolved in 40 mL of water and extracted (4 x 50 ml) with methylene chloride. The organic layers are dried over sodium sulfate a~d the~ evaporated to dryness under vacuum to give the product.
20 Exa~ple 3 Preparatio~ Of 2,5-Bis(2,2,3,3,4,4,4-heptafluoro-1-l,y.l~u,.yLltyl)pyrrole Heptafluorobutyraldehyde hydrate (5 . O g, 23 mmol) was placed in a 100 mL Schlenk flask. This was frozen with 25 liquid nitrogen and an inert atmosphere was established.
Against an outflow of nitrogen, dried pyrrole (0.694 mL, 10 mmol) and sodium hydroxide (2.25 g, 56 mmol) were added. The flask was wrapped in foil and the mixture was stirred for 2 days. The volatiles were removed ~y vacuum, leaving a light 30 brown, oily solid. The solid was dissolved in 40 mL of water and the solution was extracted (4 x 50 ml) with methylene chloride. The organic layers were dried~ over sodium sulfate and then evaporated to dryness under vacuum to an oily brown solid (38%), which proved to be a diastereomeric mixture of 35 the desired products. ~ ~ :
_ _ _ _ _ _ _ _ _ _ . _ ~ Wo95/29916 21 8 7 9~ r~.,. .3~

Example 4 Preparation Of 2-(2,2-Difluoro-2-p~nt~f~ yhL.Iyl-~ .1LO-y~thyl)pyrrole 2-Pentafluorophenyl-2,2-difluoroethanal (40 mmol) 5 and THF (5 ml) are placed in a 100 mL Schlenk flask. This is frozen with liquid nitrogen and an inert atmosphere is est~hl; ~h~d. Against an outflow of nitrogen, dried pyrrole (5.95 mL, 85.8 mmol) and sodium hydroxide (4.52 g, 113 mmol) is added. The flask is wrapped in foil and the IrLixture is 10 stirred overnight. The volatiles are removed by vacuum, the resulting solid is dissolved in 40 mL of water, and the solution is extracted (4 x 50 ml) with methylene chloride.
The organic layers are dried over sodium sulfate and then evaporated to dryness under vacuum to give 2- (2, 2-difluoro-2-15 pentafluorophenyl-1-hydroxyethyl)pyrrole.
2xample 5 Preparation Of 2-(2,2,2-Trifluoro-l-hy~L~ y~:thyl~pyrrole The procedure of Example 4 is repeated except that trifluoroacetaldehydeisusedinplaceof 2-Pentafluorophenyl-20 2, 2-difluorf~eth;~n;~
Example 6 Preparation of 2-Pyrrolylperfluorou~decyl Methanol The procedure of Example 4 is repeated except that perfluorododecanal is used in place of 2-Pentafluorophenyl-25 2, 2-difluoroethanal.
Example 7 Preparation Of Tetrakis(heptafluoL.~pr~21)p~Ly~LyLLn From 2-Pyrrolyperfluo~,yr~,yyl Methanol Benzene (650 ml) was placed in a one liter, double-30 necked flask and azeotropically dried under nitrogen using arecycling Dean-Stark apparatus. p-Tol~ n~s~ll fonic acid hydrate (50 mg) was added to the benzene and azeotropic distillation was c~ntlnll~f~ until the distillate stopped phase separating. The Dean-Stark trap was emptied and 4A molecular _ _ _ _ .. . .. . _ _ _ .. .. , , .. , . . _ _ . _ WO9~/29916 ~ 87949 p~"~ ~

sieves ( 2 o ml ) were added to _ the trap . Distillation was c~nt;nllP~l for 10 minutes with the distillate recycling through the molecular sieve6. 2-PyrrolylperfluoLul,Lu~ylmethanol (265 mg, 1 mmol) was dissolved in 10 ml of dry benzene and added 5 (all at once) to the benzene solution heated at reflux. The solution became pink immediately after the addition, then gradually darkened. 31eating was c nnt;nllpd for 30 minutes and the reaction mixture was quenched with 600 mg of DDQ. Heating was . .,nt;nllPd for an additional hour under N2. The solution 10 was transferred to a 1 liter round bottom flask and the solvent was removed and recovered by rotary evaporation. The L. ;n;n~ dark brown residue was dissolved, to the extent possible, in 50 ml of warm hexane ,-~nt~;n;ng 1 ml of pyridine, and was poured directly on to a short (2 x 10 cm) column 15 consisting of silica that was packed in hexane and topped with a 2 cm pad of Celite. Elution of the porphyrin was carried out with hexane. rollprt;on was continued until the Pluant became nearly colorles6. The solvent was removed from the collected fraction and the resulting solid was washed with 20 cold hexane (10 ml) and filtered to yield 90 mg (3796) of nearly pure 5, 10, 15, 20-tetrakis (per~luoropropyl) porphyrin.
An analytical sample was recrystallized from chloroform (-20OC) to yield crystals suitable for X-ray diffraction. lH
NMR (360 ~z, CDC13) d 9.50~ (s, 8 H); -2.30 (s, 2 H) . l9F NMR
2~ (DCD13 CF3CûOH ext. std) d -79.7 (t, 3 F); -80.9 (broad s, 2 F); -118.8 (broad s, 2 F). The l9F spectrum shows evidence of exchange behavior. The signal at -llR.R ppm sharpens to a broadened triplet upon warming the solution to 55C. l'C NMR
(75 MHz, CDCl3) gave only two ~ Prn~hle signals at 144.2 and 30 133 . 8 after a 16 hour run.
Example 8 Preparation O~ Tetrakis (hepta~luuL~.~L~yl)porphyrin From Pyrrole And ~eptafluoroL,ulyL~ldehyde In a procedure ~analogous to that described in 35 Example 7, the apparatus was charged with benzene (650 ml), p-toluenesulfonic acid hydrate (50 mg) and ~ W095129916 2 ~ 8 7949 P~ . 5 --heptafluorobutyraldehyde hydrate (0.22g, 1 mmol). After refluxing the mixture for 1 hour, dry pyrrole (70 ~1, 1 mmol) was added. The reaction was monitored by thin layer chromatography (TLC); after 1.5 hours the reaction was 5 quenched as in Example 7. The reaction mixture was neutralized with pyridine, filtered through silica gel, pumped dry, and further purified by C~lLI ~ raphy on silica.
Several pyrrole-cr~n~;n;n~ products can be isolated from this preparation . The desired product, 10 tetrakis(heptafluoro)porphyrin, eluted as the first colored band. This method gives 4 mg (1. 6~) of the target porphyrin.
~!xample 9 Preparation Of Tetrachlor~ ~hine Porphine (Zn) (40 mg) was dissolved in 300 mL of a 15 1:1 mixture of THF and CHC13, and the mixture was placed in a 500 ml round bottomed flask. N-chloros~ ;n1m;de (NCS) was added (4.2 eq. ) and the mixture was stirred overnight protected from the lig~t. The reaction was monitored by TLC
and four intermediates were observed, presumably the target 20 compound and the mono-, di-, and trichloro inteL ~ t~.
After 24 hours the reaction was stopped and tetrachloroporphine (> 8096) was isolatea.
Example 10 Preparation Of Co~acial Porphyrin Dimers To a THF solution of 5-bromo-10,15,20-trichloroporphyrinate (Zn) (1 eq. ) is added Pd bis (triphenylphosphine) (5 mol9~) and anthracene-1, 8-bis (chlorozinc) (0.5 eq) . The reaction is stirred for 24 hours at room temperature. One band is evident by TLC of the 30 reaction mixture. The compound is purified by silica gel chromatography to isolate the dimeric, anthracene bridged compound .
Those skilled in the art will appreciate that numerous changes and modif ications may be made to the 35 preferred embodiments of the invention and that such changes WO9~/29916 2t 81~49 and modifications may be made without departing from the spirit of the invention. For example, it is believed that the methods of the present invention can be practiced using porphyrin-related cn~mlnr~q such as chlorins, phorbins, 5 bacteriochlorins, porphyrinogens, sapphyrins, texaphrins, and pthalocyanines in place of porphyrins. It is therefore intended that the ~rp~nA~cl claims cover all such e~auivalent variations as fall within the true spirit and scope of the inventioL .

Claims (40)

WHAT IS CLAIMED IS:
1. A synthetic process comprising the steps of:
(a) contacting an aldehyde having formula RA-CHO
with a pyrrole derivative having formula:
in organic solvent in the presence of acid for a time and under conditions effective to form a reaction mixture comprising water and an adduct of said aldehyde and said pyrrole derivative; and (b) removing from said reaction mixture a portion of said water;
wherein:
at least one RA is a group that is electron-withdrawing relative to hydrogen;
at least one R? is H or an acid-stable functional group; and q is 0, 1, or 2.
2. The process of claim 1 wherein RA is alkyl having 1 to about 30 carbon atoms, aryl having 3 to about 50 carbon atoms, N- (alkyl) 3+, NH3+, NO2, SO2- (alkyl), CN, SO2-(aryl), C(O)OH, F, Cl, Br, I, C(O)O- (alkyl), C(O) - (alkyl), or CHO, wherein alkyl groups have from about 1-30 carbon atoms and aryl groups have about 3 - 50 carbon atoms.
3. The process of claim 1 wherein RA is haloalkyl having 1 to about 20 carbon atoms or haloaryl having 6 to about 20 carbon atoms.
4. The process of claim 1 wherein RA is perfluoroalkyl having 5 to about 20 carbon atoms or perfluoroaryl having 6 to about 20 carbon atoms.
5. The process of claim ? wherein said solvent is nonpolar and aprotic.
6. The process of claim ? wherein said solvent forms an azeotrope with water.
7. The process of claim ? wherein said solvent is benzene, toluene, xylenes, methylene chloride, chloroform, trichloroethylene, or a mixture thereof.
8. The process of claim ? wherein said acid is a non-volatile, protic acid.
9. The process of claim ? wherein said acid is benzoic acid, p-toluenesulfonic acid, methanesulfonic acid, trifluoracetic acid, boron trifluoride, boron trichloride, or a mixture thereof.
10. The process of claim ? wherein a catalytic amount of said acid is used.
11. The process of claim 6 wherein said water is removed by distilling said azeotrope.
12. The process of claim 11 further comprising collecting said distilled azeotrope in a vessel such that said distilled azeotrope forms a substantially aqueous phase and a substantially organic phase.
13. The process of claim 12 further comprising returning said substantially organic phase to said reaction mixture.
14. The process of claim 11 further comprising contacting said distilled azeotrope with a drying agent for a time sufficient to remove a portion of said water contained therein.
15. The process of claim 14 further comprising returning said dried distillate to said reaction mixture.
16. The process of claim 14 wherein said drying agent comprises phosphorous pentoxide, calcium hydride, calcium oxide, barium oxide, lithium aluminum hydride, molecular sieves, or a mixture thereof.
17. The process of claim 11 further comprising adding organic solvent to said reaction mixture.
18. The process of claim 1 further comprising oxidizing said reaction mixture.
19. The process of claim 1 further comprising isolating from said reaction mixture a composition containing a porphyrinogen having formula:
20. The process of claim 19 further comprising oxidizing said porphyrinogen for a time and under reaction conditions effective to form a corresponding porphyrin.
21. The product of the process of claim 1.
22. The product of the process of claim 18.
23. The product of the process of claim 20.
24. A synthetic process comprising the steps of:
(a) contacting an alcohol having formula:
with a pyrrole having formula.
in organic solvent in the presence of acid for a time and under conditions effective to form a reaction mixture comprising water and an adduct of said alcohol and said pyrrole; and (b) removing from said reaction mixture a portion of said water;
wherein:
at least one RA is a group that is electron-withdrawing relative to hydrogen;
at least one RB is H or an acid-stable functional group; and n is 0, 1, or 2.
25. A synthetic process comprising the steps of:
(a) reacting an alcohol having formula:
in organic solvent in the presence of acid for a time and under conditions effective to form a reaction mixture comprising water and an adduct of said alcohol; and (b) removing from said reaction mixture a portion of said water;
wherein:
at least one RA is a group that is electron-withdrawing relative to hydrogen;
at least one RB is H or an acid-stable functional group; and n is 0, 1, or 2.
26. A compound having formula:
wherein:
at least one RA is a group that is electron-withdrawing relative to hydrogen;
at least one RB is H or an acid-stable functional group; and q is 1 or 2.
27. The compound of claim 26 wherein RA is alkyl having 1 to about 30 carbon atoms or aryl having 3 to about 50 carbon atoms.
28. The compound of claim 26 wherein RA is haloalkyl having 1 to about 20 carbon atoms or haloaryl having 6 to about 20 carbon atoms.
29. The compound of claim 28 wherein RB is H, perhaloalkyl, perhaloaryl; NO2, F, Cl, Br, or CN.
30. The compound of claim 26 wherein RA is perhaloalkyl having 5 to about 20 carbon atoms or perhaloaryl having 6 to about 20 carbon atoms.
31. A compound having formula:
wherein:
at least one RA is a group that is electron-withdrawing relative to hydrogen;
at least one RB is H or an acid-stable functional group; and n is 0, 1, or 2.
32. A compound having formula:
wherein:
at least one RA is a group that is electron-withdrawing relative to hydrogen;
at least one RB is H or an acid-stable functional group; and n is 0, 1, or 2.
33. A compound having formula:
wherein:
at least one RA is an alkyl group that is electron-withdrawing relative to hydrogen; and at least one RB is H or an acid-stable functional group.
34. A compound having formula (1), (2), or (3):
(1) (2) (3) wherein:
at least one RA is an alkyl group that is electron-withdrawing relative to hydrogen;
at least one RB is H or an acid-stable functional group; and M and M' are metal atoms.
35. A polymer comprising a plurality of linked porphyrin units, wherein:
each of said porphyrin units, independently, has formula (1), (2), or (3);
M and M' are metal atoms;
at least one RA is an alkyl group that is electron-withdrawing relative to hydrogen; and at least one of RA and RB includes a linking group that is:
aryl having 3 to about 50 carbon atoms, [C(RC)=C(RD)(RE)]x, [CC(RD)]x, [CH2(RC)-CH(RD)(RE)]x or [CH=CH(RD)]x where n is at least 1, where RC, RD, and RE are, independently, H, F, Cl, Br, I, alkyl having from 1 to about 30 carbon atoms, aryl having about 3 to about 50 carbon atoms, alkenyl having from 1 to about 30 carbon atoms, alkynyl having from 1 to about 30 carbon atoms, trialkylsilyl, porphyrinato or a chemical functional group comprising a peptide, nucleoside or saccharide; or cycloalkyl or aryl having about 10 to about 22 carbon atoms.
36. In a process in which an alkane or alkene is selectively oxidized by contact with air or oxygen in the presence of a compound according to claim 33.
37. The process of claim 36 wherein said alkane or said alkene is dissolved in supercritical carbon dioxide.
38. In a process in which an alkane is selectively oxidized by contact with an oxidant in the presence of a catalyst comprising a Group IV(a) to VII transition metal coordination complex, the improvement wherein said complex comprises a compound according to claim 33.
39. A supported catalyst comprising a compound according to claim 33 on a solid support material.
40. A composition comprising a polymeric matrix that contains at least one compound according to claim 33.
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US5405957A (en) * 1992-10-30 1995-04-11 The University Of British Columbia Wavelength-specific photosensitive compounds and expanded porphyrin-like compounds and methods of use
US5241062A (en) * 1993-01-19 1993-08-31 Sun Company, Inc. (R&M) Synthetic route to meso-tetra hydrocarbyl or substituted hydrocarbyl porphyrins and derivatives

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US5856515A (en) 1999-01-05
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EP0757690A4 (en) 1999-06-16

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