EP0660834A1 - Nouveaux derives de fullerenes, leur procede de fabrication et leur utilisation - Google Patents

Nouveaux derives de fullerenes, leur procede de fabrication et leur utilisation

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Publication number
EP0660834A1
EP0660834A1 EP93919187A EP93919187A EP0660834A1 EP 0660834 A1 EP0660834 A1 EP 0660834A1 EP 93919187 A EP93919187 A EP 93919187A EP 93919187 A EP93919187 A EP 93919187A EP 0660834 A1 EP0660834 A1 EP 0660834A1
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EP
European Patent Office
Prior art keywords
compound
reaction
fullerene
toluene
addition
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.)
Withdrawn
Application number
EP93919187A
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German (de)
English (en)
Inventor
Klaus-Dieter Kampe
Hans-Ulrich Ter Meer
Norbert Karl Egger
Martin Anton Vogel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Siemens Axiva GmbH and Co KG
Original Assignee
Hoechst AG
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Filing date
Publication date
Priority claimed from DE19924229979 external-priority patent/DE4229979A1/de
Priority claimed from DE19934312632 external-priority patent/DE4312632A1/de
Application filed by Hoechst AG filed Critical Hoechst AG
Publication of EP0660834A1 publication Critical patent/EP0660834A1/fr
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D245/00—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms
    • C07D245/04—Heterocyclic compounds containing rings of more than seven members having two nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F25—REFRIGERATION OR COOLING; COMBINED HEATING AND REFRIGERATION SYSTEMS; HEAT PUMP SYSTEMS; MANUFACTURE OR STORAGE OF ICE; LIQUEFACTION SOLIDIFICATION OF GASES
    • F25D—REFRIGERATORS; COLD ROOMS; ICE-BOXES; COOLING OR FREEZING APPARATUS NOT OTHERWISE PROVIDED FOR
    • F25D13/00—Stationary devices, e.g. cold-rooms
    • F25D13/06—Stationary devices, e.g. cold-rooms with conveyors carrying articles to be cooled through the cooling space
    • F25D13/067—Stationary devices, e.g. cold-rooms with conveyors carrying articles to be cooled through the cooling space with circulation of gaseous cooling fluid
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F25—REFRIGERATION OR COOLING; COMBINED HEATING AND REFRIGERATION SYSTEMS; HEAT PUMP SYSTEMS; MANUFACTURE OR STORAGE OF ICE; LIQUEFACTION SOLIDIFICATION OF GASES
    • F25D—REFRIGERATORS; COLD ROOMS; ICE-BOXES; COOLING OR FREEZING APPARATUS NOT OTHERWISE PROVIDED FOR
    • F25D25/00—Charging, supporting, and discharging the articles to be cooled
    • F25D25/04—Charging, supporting, and discharging the articles to be cooled by conveyors
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01B—CABLES; CONDUCTORS; INSULATORS; SELECTION OF MATERIALS FOR THEIR CONDUCTIVE, INSULATING OR DIELECTRIC PROPERTIES
    • H01B1/00—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors
    • H01B1/06—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors mainly consisting of other non-metallic substances
    • H01B1/12—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors mainly consisting of other non-metallic substances organic substances
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/70—Nanostructure
    • Y10S977/734—Fullerenes, i.e. graphene-based structures, such as nanohorns, nanococoons, nanoscrolls or fullerene-like structures, e.g. WS2 or MoS2 chalcogenide nanotubes, planar C3N4, etc.
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/70—Nanostructure
    • Y10S977/734—Fullerenes, i.e. graphene-based structures, such as nanohorns, nanococoons, nanoscrolls or fullerene-like structures, e.g. WS2 or MoS2 chalcogenide nanotubes, planar C3N4, etc.
    • Y10S977/735—Carbon buckyball
    • Y10S977/737—Carbon buckyball having a modified surface
    • Y10S977/738—Modified with biological, organic, or hydrocarbon material
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/70—Nanostructure
    • Y10S977/832—Nanostructure having specified property, e.g. lattice-constant, thermal expansion coefficient
    • Y10S977/835—Chemical or nuclear reactivity/stability of composition or compound forming nanomaterial
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/84—Manufacture, treatment, or detection of nanostructure
    • Y10S977/895—Manufacture, treatment, or detection of nanostructure having step or means utilizing chemical property
    • Y10S977/896—Chemical synthesis, e.g. chemical bonding or breaking
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/902—Specified use of nanostructure

Definitions

  • the invention relates to new addition compounds of diamines on fullerene C ⁇ 0 and / or C 70 and methods for their preparation and their use.
  • .C ⁇ 0 is a polyfunctional molecule, and the formation of complex, conventional methods is not a major disadvantage of the reported reactions separable mixtures in the reaction of the polyfunctional C 60 with amines In almost every case, a myriad of different reaction products are formed in the manner of the reactions carried out so far, from which pure individual substances should be isolated, if at all, only with unreasonably great effort [ A. Hirsch, Angew. Chem. 104 (1992), 808].
  • the invention thus relates to addition compounds obtainable by reaction of diamines of the general formula I,
  • R 1 (C 2 -C 4 ) alkylene or 1, 2- or 1, 3-cyclo- (C 3 -C 7 ) alkylene and
  • R 2 and R 3 are independently hydrogen or or
  • R 2 and R 3 together represent (C 2 -C 4 ) alkylene, with fullerene C ⁇ 0 and / or C 70 .
  • the diamine of the formula I is bound via its two nitrogen atoms to adjacent C atoms of a bond between the six-membered ring of the football-like fullerene structure, ie on the fullerene surface. This bond between two S «wedding rings of C ⁇ 0 or C 70 is referred to below as the" 6-6 bond ".
  • the structure of the diaddition compounds which are obtained as regioisomers is analogous to that of the monoadducts; due to the polyfunctionality of the C eo and C 70 , a number of regioisomeric diaddition compounds are possible.
  • the mass spectra and the 1 H and 13 C NMR spectra of the diadducts demonstrate that fully dehydrated fullerene derivatives are also present in these, ie both hydrogen atoms introduced per diamine of the formula I have been eliminated. This means that there are no hydrogen atoms attached to the fullerene structure.
  • a structure of a diaddition compound, in which R 2 and R 3 have the meaning given for formula I, is shown in formula III as an example of a structure chosen arbitrarily from the regioisomeric structures.
  • the structure of the diaddition compound of formula III is arbitrary in terms of the relative spacing of the diamine units. A number of other relative structures are possible for diaddition compounds.
  • the reaction according to the invention is advantageously carried out with pure fullerene C ⁇ 0 or C 70 or with fullerenes whose content is at least 95% of C ⁇ 0 or C 70 .
  • the reaction according to the invention is preferably carried out with> 95% C ⁇ 0 or pure C ⁇ 0 .
  • the reaction according to the invention with diamines of the formula I is preferred
  • R 2 and R 3 independently of one another are hydrogen, CH 3 or C 2 H 5 or
  • R 2 and R 3 together mean - (CH 2 ) 2 - or - (CH 2 ) 3 -.
  • N, N'-dimethylethylenediamine are particularly preferred for the reaction according to the invention as diamine; N-methyl-N'-ethylethylenediamine; N, N'-diethylethylenediamine; N, N'-dimethyl-trimethylene diamine; Piperazine, homopiperazine, N-methyl-ethylenediamine and N-ethyl-ethylenediamine.
  • the reaction according to the invention between the diamine of the general formula I and C ⁇ 0 and / or C 70 is preferably carried out in solution, ie the fullerene to be reacted is preferably subjected to the addition reaction in dissolved form.
  • Suitable solvents are all those in which fullerene C ⁇ 0 and / or C 70 is noticeably soluble.
  • Aromatic hydrocarbons, halogen compounds or ethers such as, for example, benzene, toluene, xylenes, mesitylene, (C 2 -C 4 ) alkylbenzenes, tetralin, naphthalene, 1- and / or 2-methylnaphthalene, dimethylnaphthalenes, (C.
  • Aromatic hydrocarbons and / or halogen compounds which can be conveniently distilled out of the reaction mixture under normal pressure or under vacuum at temperatures up to 150 ° C. and anisole are preferred.
  • solvents can be mixed into the aromatic solvents, expediently in such an amount that a noticeable solubility of fullerene C ⁇ 0 and / or C 70 is retained.
  • admixable solvents are aliphatic and / or cycloaliphatic hydrocarbons which are liquid at room temperature and boil below 150 ° C., mono-, di-, tri- and / or tetrachloroalkanes and / or alkenes.
  • tertiary amines such as. B. 1, 4-diazabicyclo [2.2.2] octane, as basic additives, in molar proportions of 0.05 to 8.0 based on C 60 and / or C 70 .
  • These basic additives are advantageous if only a small or no molar excess of the diamine of the formula I compared to C 60 and / or C 70 is used.
  • These possible basic additives increase the reaction rate while maintaining a favorable selectivity with regard to the formation of monoaddition products.
  • the molar ratio used between the diamine and the respective fullerene influences the composition of the fullerene-diamine addition products, to the extent that when the diamine concentration is increased compared to the amount of fullerene used, the proportion of multiple addition products increases.
  • the monoaddition product and diaddition products are the main products.
  • the ratio in which the monoaddition, diaddition and multiple addition or reaction products are formed also depends heavily on the structure of the diamine of formula I used.
  • the monoreaction product is predominantly formed within the above-mentioned range (0.5 to approximately 20.0) of the molar ratio of diamine to fullerene.
  • N, N'-dimethyl In contrast, ethylenediamine forms monoreaction product and direaction product in comparable amounts as the main products under these conditions.
  • the multiple reaction products outweigh mono and direaction products in the reaction according to the invention under comparable reaction conditions.
  • the reaction according to the invention of a diamine of the formula I with fullerenes C 60 and / or C 70 can be carried out within a very wide temperature range.
  • the reaction can be carried out between -30 ° C, preferably 0 ° C, and + 300 ° C, preferably + 160 ° C.
  • the reaction can also take place at temperatures above or below.
  • the reaction according to the invention can be carried out within a very wide concentration range, based on the concentration of C ⁇ o and / or C 70 and the concentration of the diamine of the formula I in the particular solvent or solvent mixture. This concentration range extends from approximately 10 "3 millimolar to the saturation concentration of C ⁇ 0 or C 70 in the solvent or solvent mixture used in each case. However, the reaction can also be carried out at a fullerene concentration of ⁇ 10 3 millimolar or in the presence of undissolved fullerene C ⁇ 0 and / or C 70 are executed.
  • the concentration of the diamine of the formula I in the reaction medium is determined via the molar ratio.
  • the reaction times in the reaction according to the invention can vary within a very wide range. On the one hand, there is the well-known relationship between reaction time and reaction temperature in chemistry, in that the necessary reaction time is shortened with increasing reaction temperature.
  • the required reaction time also depends on the concentration of the reactants, the diamine and C ⁇ o and / or C 70 , in the reaction medium and also on their mutual molar ratio. In general, the higher the concentrations of the reactants in the reaction medium and the greater the molar ratio between the diamine and C ⁇ 0 and / or C 70 , the shorter the time required for the reaction. Since this molar ratio in turn influences the resulting product spectrum of the addition products according to the invention, the intended course of the reaction, ie the resulting product spectrum, can be controlled via this molar ratio and the reaction time.
  • the required reaction time and the proportion of the predominant monoadduct increases strong.
  • the monoadduct can thus, under certain conditions, become the quasi-only reaction product. become.
  • a preferred embodiment of the reaction according to the invention therefore consists in that a 0.2-5.0 millimolar solution of C ⁇ 0 and / or C 70 in an aromatic hydrocarbon, fluorine or chlorinated hydrocarbon or anisole which is liquid at room temperature or a mixture which is liquid at room temperature from such aromatic solvents, add 0.5-10 times, preferably 0.5-5 times, the molar amount of a diamine of the formula i and this mixture for 0.3 to 30 days, preferably 2-14 days, at a temperature between 0 ° C, preferably 20 ° C, and 160 ° C, preferably 110 ° C, leaves.
  • the well-known relationship applies that the higher the reaction temperature chosen, the shorter the reaction time.
  • Particularly preferred solvents are benzene, toluene, xylene, chlorobenzene, 1, 2 and / or 1, 3-dichlorobenzene and / or anisole.
  • the behavior in chromatography serves to characterize the new compounds formed.
  • the number of base equivalents per defined new adduct also characterize, in conjunction with the chemical composition, the new compounds according to the invention.
  • the chemical composition of the new fullerene derivatives according to the invention is evident from the elementary analyzes. In the case of uniform adducts according to the invention, these show from a diamine of the formula I at C 1 and / or C 70 whether a mono or a multiple adduct, for example a di, tri, tetra, penta or hexa adduct or a higher one Adduct is present.
  • the spectroscopic data of the new compounds according to the invention serve in a particular degree to uniquely characterize them. These include the absorption spectra in the UV, visible and IR range.
  • the uniform addition compounds according to the invention show characteristic IR spectra with a sharp band structure.
  • the compounds according to the invention each have characteristic UV absorptions, so they differ in the position of their maxima.
  • the mass spectra recorded in FABMS technology also characterize the respective compounds and, if available or recognizable by the mol peak, confirm the molecular weights.
  • the NMR spectra measured both as solid spectra and as solution spectra, also serve to characterize and assign the structure of the compounds according to the invention.
  • the IR spectrum of a monoaddition or diaddition compound of a diamine I according to the invention shows no NH band at C 60 .
  • This characteristic proves that both nitrogen atoms of the diamine of the formula I are linked to carbon atoms of the fullerene.
  • the new fullerene addition compounds formed according to the invention can be dissolved and / or undissolved in the reaction mixture depending on the solvent or solvent mixture used and the temperature.
  • the reaction according to the invention which, at a total concentration of both reactants (starting materials), ie fullerene C ⁇ 0 and / or C 70 and the diamine of the formula I, of ⁇ 25 mmolar in benzene, toluene, xylene, tetralin, ethylbenzene, 1 , 2-dichlorobenzene and / or anisole are carried out with or without the addition of naphthalene, the new mono- and diaddition compounds formed are generally dissolved or largely dissolved at a temperature between 0 ° C. and 110 ° C.
  • the new addition compounds formed primarily the monoaddition compounds, can be partially deposited as crystalline substances by concentrating the reaction solution and as such in the usual way, for. B. by filtration.
  • a preferred embodiment for the isolation and purification of the addition compounds according to the invention is that the reaction mixture is separated either directly or after prior filtration by column chromatography, preferably on silica gel, into optionally unreacted fullerene C ⁇ 0 and / or C 70 and the addition compounds formed.
  • Column chromatography on silica gel with toluene and dichloromethane and dichloromethane / methanol mixtures is advantageously carried out as the mobile phase.
  • fullerene C ⁇ 0 and / or C 70 is eluted, if still present. Then follows the sharply delineated the respective monoaddition product and followed by this at a clear distance, since polar, optionally formed di- and multiple addition compounds.
  • RP reversed phase
  • the addition compounds according to the invention are obtained as solid, often crystalline substances.
  • the latter applies in particular to the mono- and diaddition compounds.
  • it is characterized in particular by the action of piperazine (R 1 and R 2 and R 3 together each - (CH 2 ) 2 -) on C ⁇ formed mono addition product from large crystallization tendency.
  • the separation, isolation and purification of the compounds according to the invention does not rely on the use of HPLC technology
  • the HPLC technology is suitable for characterizing the addition compounds obtained according to the invention. Retention time coupled with the stationary and the liquid phase used, the flow rate and the Conventional column parameters serve as reliable material parameters for the characterization of pure substances or mixtures according to the invention.
  • reaction mixture which can be worked up by column chromatography according to the invention is that any unreacted C ⁇ 0 and / or C 70 can be separated off simply and cleanly and can thus be recovered for reuse. In view of the high price of fullerene C ⁇ 0 and / or C 70, this is of considerable importance.
  • the addition compounds of diamines of the formula I, in which R 2 and R 3 have the meaning given above, at C ⁇ 0 and / or C 70, which are obtainable according to the present invention, are basic compounds and form acid addition salts with protonic acids, per unit of fullerene C ⁇ 0 and / or C 70 added diamine at least 1 equivalent of acid.
  • a monoaddition compound can bind at least 1 and a diaddition compound at least 2 equivalents of acid with the formation of acid addition salts.
  • hydrochloric acid z. B. a hydrochloride is formed from the monoaddition compound of piperazine at C ⁇ 0 .
  • the acid addition salts are considerably less soluble in non-polar solvents than the associated bases. So z. B. from a solution of the monoaddition product formed from piperazine and Cgg in anisole with the addition of ethereal hydrochloric acid the corresponding hydrochloride almost quantitatively.
  • fullerene derivatives according to the invention are suitable for use as complex ligands. In this capacity, they can be used to modify catalysts.
  • the compounds according to the invention can be used to inhibit enzymes, for example to inhibit HIV (human immunodeficiency virus) enzymes, such as HIV-1 protease, with which they represent biological active substances which can be used, for example, as antiviral agents.
  • HIV human immunodeficiency virus
  • addition connections are electrically conductive in the solid state.
  • This material can be used to apply conductive coatings from solution, for example.
  • the monoaddition compound obtained by the action of piperazine on C ⁇ 0 shows intrinsic conductivity.
  • the unspecified solvent mixtures used in column chromatography are CH 2 CI 2 / CH 3 OH mixtures.
  • the Raman spectrum of this monoaddition product is shown in FIG. 2.
  • This monoaddition product of piperazine at C ⁇ 0 ( ⁇ or as addition compound No. 1) can be recrystallized from solvents and further purified in this way. It crystallizes in thin, long, dark-colored, highly reflective needles.
  • Suitable solvents for this purpose are chlorobenzene, dichlorobenzene and / or anisole.
  • the new compound (No. 1) is sparingly soluble or quasi-insoluble in benzene, toluene, CHCI 3 , CH 2 CI 2 and CH 3 OH, and soluble in CS 2 .
  • HPLC column, eluent as for addition compound no. 1, flow 0.8 ml / min.
  • Retention time 3.09 or 3.12 min. (Area% 98.4).
  • a molar mass M 888 Dalton results from the mass spectrum, indicated by an intense M ⁇ peak at m / z 888.
  • a molecular mass M 888 Dalton results from the mass spectrum, indicated by an intense MH e peak at m / z 889.
  • the IR spectrum of the pure diaddition compound no. 5 is shown in FIG. 8, the UV spectrum in FIG. 7 reproduced.
  • Example 6 a mixture of toluene and tetrahydrofuran (THF) was used as the solvent and in Example 10, a mixture of toluene and tetrachlorethylene.
  • the diaddition compounds (No. 2) No. 2, 3, 3a, 4 and 5) eluted in the respective column chromatography after the monoaddition compound (from piperazine at C ⁇ 0 ) (No. 1) were combined in each case, ie not into the individual diaddition compounds 2, 3, 3a , 4 and / or 5 separated.
  • Hydrochloride of the monoaddition compound of piperazine at C ⁇ 0 81 mg (0.1 mmol) of the monoaddition compound (addition compound No. 1) of piperazine at C ⁇ 0 were dissolved in 30 ml of anisole at 110 ° C. This solution was cooled to 50 ° C without stirring. At this temperature, 0.36 ml of a 0.61 molar solution of HCl in ether was added with stirring (under the liquid surface). Solid flocculated immediately as a light brown precipitate. The mixture was stirred for a further 30 minutes, the temperature dropping from 50 ° C.
  • a molecular mass M 888 Dalton results from the mass spectrum, indicated by an intense MH ⁇ peak at m / z 889.
  • a molar mass M 888 Dalton results from the mass spectrum, indicated by an intense MH ⁇ peak at m / z 889 or an M ⁇ peak at m / z 888.
  • a molar mass M 888 Dalton results from the mass spectrum, indicated by an intense M ⁇ peak at m / z 888 or MH ⁇ peak at m / z 889.
  • the mixture was then eluted further with CH 2 CI 2 / CH 3 OH (100: 0.2 to 0.4).
  • 1000 ml of eluate containing a brown-black migrating zone were selected.
  • the new compound (No. 7) is poorly soluble in CS 2 in benzene, toluene, CHCI 3 , CH 2 CI 2 and CH 3 OH.
  • addition compound No. 8 After the main product described above ( ⁇ addition compound No. 7) was eluted from the column, elution was continued with CH 2 CI 2 / CH 3 OH (100: 1). After 500 ml of substance-free eluate, 15 mg of a further addition compound of homopiperazine at C ⁇ 0 ( see addition compound no. 8) were eluted with 1000 ml (100: 1, 5), which was obtained in crystalline form after digestion with ether. After suction and drying (50 ° C, 3 mb) of the crystals, 13 mg of addition compound No. 8 were obtained. TLC (CH 2 CI 2 / C 2 H 5 OH 10: 1) R F : 0.52 to 0.56
  • HPLC column, eluent and flow as for addition compound No. 7, retention time in min (area%): 5.81 (64.1%); 6.09 (15.3%) and 6.25 (20.6%). HPLC thus shows that addition compound No. 8 consists of 3 components. There are 3 regioisomers
  • the reaction mixture is filtered through a filter aid and the filtrate is drawn up onto a silica gel S (0.063 to 0.2 mm) toiuole column (H: 64; 0 3.4 cm) or filtered through it.
  • a silica gel S 0.063 to 0.2 mm toiuole column (H: 64; 0 3.4 cm) or filtered through it.
  • elution was continued with 500 ml of toluene and 500 ml of CH 2 Cl 2 .
  • This monoaddition product of N, N'-dimethylethylenediamine at C ⁇ 0 ( ⁇ or as monoaddition compound No. 12) can be recrystallized from solvents and further purified in this way.
  • Suitable solvents for this purpose are dichlorobenzene, chlorobenzene and / or anisole and CS 2 .
  • the new compound (No. 12) is sparingly soluble or quasi-insoluble in benzene, toluene, CHCI 3 , CH 2 CI 2 and CH 3 OH, and readily soluble in CS 2 .
  • Diaddition compounds No. 13A to No. 13C have the following R F values:
  • the diaddition compounds No. 14 - No. 16 have the following R F values: No. 14 15 16
  • the IR spectrum (KBr) of this compound no. 17 is shown in FIG. 22 reproduced.
  • the mass spectrum (FAB) shows a strong MH ⁇ or strong M ⁇ peak at m / z 835 or at m / z 834.
  • the IR spectrum (KBr) of this compound no. 18 is shown in FIG. 23 reproduced.
  • the mass spectrum (FAB) shows a strong MH ® or strong M ⁇ peak at m / z 821 or at m / z 820.
  • the IR spectrum (KBr) of this compound no. 20 is shown in FIG. 25 reproduced.
  • the mass spectrum (FAB) shows a strong MH ® or M ⁇ peak at m / z 807 or at m / z 806.
  • the chromatography was carried out at 0.3 bar N 2 gauge pressure analogously to Examples 1, 6 and 19.
  • the mass spectrum (FAB) of this substance shows a strong MH ® or strong M ⁇ peak at m / z 865 or at m / z 864.
  • Diaddition Compound No. 23K This substance is called Diaddition Compound No. 23K.
  • the IR spectrum (KBr) of this compound No. 23K is shown in FIG. 28 reproduced.
  • the IR spectrum (KBr) of this compound no. 24 is shown in FIG. 29 reproduced.
  • the mass spectrum (FAB) shows a strong MH ® or strong M ⁇ peak at m / z 913 or at m / z 912.
  • DC ⁇ eluent: CH 2 CI 2 / C 2 H 5 OH 10: 1): R F 0.56-0.66.

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Abstract

L'invention concerne un produit d'addition que l'on obtient en faisant réagir une diamine de la formule (I) dans laquelle R1 désigne alkylène (C¿2?-C4) ou alkylène 1,2- ou 1,3-cyclo-(C3-C7) et R?2 et R3¿, qui sont identiques ou différents, représentent alkyle (C¿1?-C3) ou hydrogène, ou bien R?2 et R3¿ représentent ensemble alkylène (C¿2?-C4), avec des fullerènes C60 et/ou C70.
EP93919187A 1992-09-08 1993-08-26 Nouveaux derives de fullerenes, leur procede de fabrication et leur utilisation Withdrawn EP0660834A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE19924229979 DE4229979A1 (de) 1992-09-08 1992-09-08 Neue Fulleren-Derivate, Verfahren zur Herstellung und deren Verwendung
DE4229979 1992-09-08
DE4312632 1993-04-19
DE19934312632 DE4312632A1 (de) 1993-04-19 1993-04-19 Neue Fulleren-Derivate, Verfahren zur Herstellung und deren Verwendung
PCT/EP1993/002306 WO1994005671A1 (fr) 1992-09-08 1993-08-26 Nouveaux derives de fullerenes, leur procede de fabrication et leur utilisation

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EP0660834A1 true EP0660834A1 (fr) 1995-07-05

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EP (1) EP0660834A1 (fr)
JP (1) JPH08503693A (fr)
AU (1) AU678387B2 (fr)
CA (1) CA2144051A1 (fr)
WO (1) WO1994005671A1 (fr)

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DE4338672A1 (de) * 1993-11-12 1995-08-17 Hoechst Ag Amino-ureido- und thioureido-fulleren-Derivate und Verfahren zu deren Herstellung
EP0695742A1 (fr) * 1994-08-03 1996-02-07 Hoechst Aktiengesellschaft Dérivés de la fullero azirine, procédé pour leur préparation et leur utilisation
TWI250874B (en) * 2000-03-24 2006-03-11 Nat Health Research Institutes Pharmaceutical compositions for preventing or treating disorders associated with bacterial or viral infection
AT410859B (de) * 2000-04-27 2003-08-25 Qsel Quantum Solar Energy Linz Verfahren zum herstellen einer photovoltaischen zelle mit einer photoaktiven schicht aus zwei organischen komponenten
WO2003029137A2 (fr) 2001-10-01 2003-04-10 Tda Research, Inc. Derivation et solubilisation de classes insolubles de fullerenes
US7812190B2 (en) 2001-10-01 2010-10-12 Tda Research, Inc. Derivatization and solubilization of fullerenes for use in therapeutic and diagnostic applications
WO2004080453A1 (fr) * 2003-03-10 2004-09-23 Mitsubishi Corporation Agent anti-virus de l'hepatite c et agent anti-vih
JP4601309B2 (ja) * 2003-03-10 2010-12-22 三菱商事株式会社 抗ｃ型肝炎ウイルス剤と抗ｈｉｖ剤
US7794682B1 (en) 2005-02-28 2010-09-14 Tda Research, Inc. Methods for fullerene recovery
KR101713127B1 (ko) 2014-05-13 2017-03-10 (주)케어젠 저색소증 개선 및 지방 형성 억제 효능을 갖는 펩타이드 및 이의 용도

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GB9203037D0 (en) * 1992-02-11 1992-03-25 Salutar Inc Contrast agents

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See references of WO9405671A1 *

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WO1994005671A1 (fr) 1994-03-17
AU678387B2 (en) 1997-05-29
CA2144051A1 (fr) 1994-03-17
JPH08503693A (ja) 1996-04-23
US5587476A (en) 1996-12-24
AU4954193A (en) 1994-03-29

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