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WO2003010361A2 - Transfert d'atomes d'azote - Google Patents

Transfert d'atomes d'azote Download PDF

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Publication number
WO2003010361A2
WO2003010361A2 PCT/CA2002/001163 CA0201163W WO03010361A2 WO 2003010361 A2 WO2003010361 A2 WO 2003010361A2 CA 0201163 W CA0201163 W CA 0201163W WO 03010361 A2 WO03010361 A2 WO 03010361A2
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Prior art keywords
group
aikyl
aryl
carbon atoms
formula
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PCT/CA2002/001163
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English (en)
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WO2003010361A3 (fr
Inventor
Andrei K. Yudin
Tung Siu
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Ylektra Inc.
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Publication date
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Priority to US10/484,843 priority Critical patent/US20050006246A1/en
Publication of WO2003010361A2 publication Critical patent/WO2003010361A2/fr
Publication of WO2003010361A3 publication Critical patent/WO2003010361A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
    • C25B3/20—Processes
    • C25B3/23—Oxidation

Definitions

  • This invention is in the field of electrochemical atom transfer, particularly the introduction of a nitrogen atom into an organic molecule in an electrochemical process.
  • the reactions of organic compounds can be classified into two broad categories: carbon-carbon bond forming processes and reactions in which carbon atoms change their oxidation states (redox processes).
  • the redox reactions in nature are accomplished by the enzyme molecules.
  • These catalysts contain metal centers that carry out the requisite electron and or atom transfer reactions.
  • the metal center of a synthetic catalyst is surrounded by a small molecule ligand that often resembles and emulates the catalytic reaction site of an enzyme.
  • One of the key roles of the ligand is to modulate reactivity at the metal center.
  • Aziridination of olefins is of particular current interest due to the enormous synthetic potential of aziridines. 1 These nitrogen-containing heterocycles have 28 kcal/mol of strain 2 and are amenable to ring-opening reactions with a wide range of nucleophiles. Such transformations lead to molecules with valuable 1,2-heteroatom relationships, commonly found in natural products and in pharmaceuticals. Olefin aziridination reactions are usually accomplished via metal-mediated transfer of a nitrene fragment to the olefin. 4 The corresponding processes can produce a variety of byproducts that stem from metal additives and from oxidants. To date, there are no examples of catalytic oxidation systems based on readily available oxidants that convert simple amines or amides into active nitrogen transfer species in the presence of olefins and leave no by-products.
  • This invention provides an electrochemical process by which a new organic molecule is obtained through the formation of a nitrogen bond.
  • An example is the formation of an aziridine by addition of the nitrogen across a double bond between two carbon atoms, in which two C-N bonds form.
  • the results of the various addition reactions shown herein can be explained in terms of the formation of a nitrene intermediate formed under the electrochemical conditions of the invention.
  • the invention is an electrochemical process for the formation of a compound having formula I:
  • the process includes a step of contacting a compound having formula II and a compound having formula III with each other in an electrolytic cell under conditions of electrolysis sufficient to form the compound of formula I.
  • A shown in these formulae is selected from the group consisting of C, N and O, and
  • R l5 R 2 , R 3 , and j can be the group consisting of aikyl, alkenyl, alkynyl, aryl, phenyl, biphenyl, and substituted aikyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of aikyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.
  • the group from which each of R 1? R 2 , R 3 , and t may be selected is the group consisting of aikyl, alkenyl, alkynyl, aryl, and substituted aikyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of aikyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.
  • the group from which each of R l5 R 2 , R 3 , and R 4 maybe selected can the group consisting of aikyl and aryl, and substituted aikyl and aryl, wherein the substituents are selected from the group of aikyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.
  • substituents can be selected from the group of halide, ketone, alcohol and ester.
  • a of starting compound II is a carbon atom
  • R 3 and j are each hydrogen, then each of ⁇ and R 2 is not hydrogen, or the double bond shown in formula II is conjugated with another olefinic double bond
  • a first carbon atom of the double bond shown in formula II is in an ⁇ -position with respect to a carbonyl group of R l5 then the second carbon atom of the double bond is not in an ⁇ -position with respect to a carbonyl group of R 3
  • II is selected from the group consisting of cyclohexene, cyclohex-2-enone, 2-methyl-pent-2-ene, 3-bromo-2-methyl-propene, trans-3- phenyl-acrylic acid methyl ester, cyclooctene, 2-methyl-buta-l,3-diene, trans-1,3- diphenylpropenone, trcr ⁇ -hex-4-en-3-one, traH5-but-2-enedioic acid dimethyl ester, trans- - phenyl-prop-2-en-l-ol, tr ⁇ «5-4-phenyl-but-3-enoic acid methyl ester, 2-(acetoxy-phenyl- methyl)-acrylic acid methyl ester, 2-(hydroxy-phenyl-methyl)-acrylic acid methyl ester, trans- 1,4-dichlorobutene, cis- 1,4-dichlorobutene
  • compound II is selected from the group consisting of cyclohexene, cyclohex-2-enone, 2-methyl-pent-2-ene, 3-bromo-2-methyl-propene, tr « «s-3-phenyl-acrylic acid methyl ester, cyclooctene, 2-methyl-buta-l,3-diene, tra «5-l,3-diphenylpropenone, trans- .ex-4- en-3-one, tr ⁇ r ⁇ s-but-2-enedioic acid dimethyl ester, tr ⁇ R5 , -3-phenyl-prop-2-en-l-ol, trans-A- phenyl-but-3-enoic acid methyl ester, 2-(acetoxy-phenyl-methyl)-acrylic acid methyl ester, 2- (hydroxy-phenyl-methyl)-acrylic acid methyl ester, trans- 1,4-dichlorobutene, cis- 1,4- dichlorobutene
  • the invention is process for the syn-addition of a nitrogen atom across a double bond.
  • the R 5 group of compound III can be selected from the specific group:
  • each of R 8 , R , R 10 , R ⁇ , R ⁇ 2 and R 13 is an organic group.
  • each of R 8 , R 9 , R 10 , R ⁇ , R 12 and R 13 can be selected from the group consisting of aikyl, alkenyl, alkynyl, aryl, phenyl, biphenyl and substituted aikyl, alkenyl, alkynyl, aryl, phenyl and biphenyl wherein the substituents are selected from the group of aikyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.
  • each of R 8 , R 9 , R 10 , R ⁇ , R 12 and R 13 can be selected from the group consisting of aikyl, aryl, phenyl and substituted aikyl, aryl and phenyl, wherein the substituents are selected from the group of aikyl, aryl, phenyl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.
  • Each of R 8 , R 9 , R 10 , R ⁇ , R 12 an R 13 preferably includes up to 20 carbon atoms, more preferably up to 18 carbon atoms, more preferably up to 16 carbon atoms, more preferably up to 14 carbon atoms, or up to 12 carbon atoms, or up to 10 carbon atoms, or up to 8 carbon atoms, or up to 6 carbon atoms.
  • Each of the substituents of the substituted groups from which R 8 , R , R 10 , R ⁇ , R 12 and R 1 can be selected is preferably selected from the group consisting of halide, ketone, alcohol and ester, and more preferably from halide, alcohol and ester.
  • the compound having formula III is N- aminophthalimide. Any of the four C-H bonds of this molecule can be replaced with substituents that would not destroy the primary amino group of this compound to be electrochemically oxidized, i.e., aikyl, aryl, halide, aikyl halide, etc.
  • the compound having formula III has a lower oxidation potential than that of a compound having formula II. It is also preferred that the compound having formula III is oxidized at a faster rate than a compound having formula II under the conditions of electrolysis of the invention.
  • the solvent the electrolytic cell can be a polar non-protic solvent, and particularly wherein the solvent can be selected from the group consisting of dichloromethane, acetonitrile, ⁇ , ⁇ -dimethylformamide, tetrahydrofuran, nitromethane, chloroform, propylene carbonate, and mixtures thereof, or other solvent suitable for conducting an electrochemical process of the invention.
  • the invention is an electrochemical process for the formation of a compound having formula IV,
  • the process includes contacting a compound having formula V and a compound having formula III with each other in an electrolytic cell under conditions of electrolysis sufficient to form the compound of formula IV.
  • (i) B is selected from the group consisting of P, S, Se and Te;
  • each of R 1 and R 15 is hydrogen or an organic group; and (iii) R 5 is NR ⁇ R 7 and each of R 6 and R 7 is an organic group.
  • the "B” is most preferably a sulfur atom, but it can be a phosphorus atom, a selenium atom, or a tellurium atom.
  • the group of organic groups from which each of R 1 , and R 15 maybe selected can be the group of aikyl, alkenyl, alkynyl, aryl, phenyl, biphenyl, and substituted aikyl, alkenyl, alkynyl, aryl, phenyl and biphenyl wherein the substituents are selected from the group of aikyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.
  • each of R 1 , and R 15 maybe selected can be the group consisting of aikyl, alkenyl, alkynyl, aryl, and substituted aikyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of aikyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.
  • each of R 14 , and R 15 maybe selected is the group consisting of aikyl and aryl, and substituted aikyl and aryl, wherein the substituents are selected from the group of aikyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane. More particularly, wherein the substituents are selected from the group of halide, ketone, alcohol and ester, and more particularly, halide, alcohol and ester.
  • the invention includes a process wherein compound V is selected from the group consisting of compounds VIII to XV:
  • compound V can be selected from any of compounds VIE to XV.
  • R 5 can be selected as described above, for reaction of compound V and III.
  • the compound having formula HT has a lower oxidation potential than that of a compound having formula II. Further, the compound having formula III is oxidized at a faster rate than a compound having formula II under the conditions of electrolysis.
  • the invention is an electrochemical process for the formation of a compound having formula VI:
  • the process involves contacting a compound having formula VII and a compound having formula III with each other in an electrolytic cell under conditions of electrolysis sufficient to form the compound of formula VI.
  • each of R 16 and R 1 is hydrogen or an organic group; and (ii) when D is a nitrogen atom, R 16 is hydrogen or an organic group, and R 17 is an electron pair.
  • the group from which each of R 16 , and R 1 may be selected can be the group consisting of aikyl, alkenyl, alkynyl, aryl, phenyl, biphenyl, etc., and substituted aikyl, alkenyl, alkynyl, aryl, phenyl, biphenyl wherein the substituents are selected from the group of aikyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.
  • each of R 16 , and R 1 is the group consisting of aikyl, alkenyl, alkynyl, aryl, and substituted aikyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of aikyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.
  • each of R 16 , and R 1 maybe selected can also be the group consisting of aikyl and aryl, and substituted aikyl and aryl, wherein the substituents are selected from the group of aikyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.
  • the substituents are selected from the group of halide, ketone, alcohol and ester.
  • the compound having formula III preferably has a lower oxidation potential than that of a compound having formula II, and preferably is oxidized at a faster rate than a compound having formula II under the conditions of electrolysis.
  • the invention involves including a carboxylate anion in the anodic cell in which the hydrazine compound II is oxidized.
  • the cell is substantially free, or even completely free, of a toxic metal catalyst.
  • Toxic metal catalysts that are to avoided include of lead cadmium, cerium, cobalt, chromium, copper, ion, mercury, iridium, manganese, molybdenum, nickel, osmium, palladium, rhenium, rhodium, ruthenium, antimony, thallium, tin and vanadium.
  • the anodic electrode is preferably a platinum electrode.
  • the acid form of the carboxylate has a first pK a
  • the anolyte solution further includes an acid having a second pK a wherein the second pK a exceeds the first pK a .
  • the carboxylate and the acid having the second pK a are solubilized in the solution and the carboxylate is provided in solution in a stoichiometric amount equal to at least half that of the hydrazine derivative, but more preferably to at least 60% that of the hydrazine derivative, or at least 70% that of the hydrazine derivative, or 80% that of the hydrazine derivative, or 90% that of the hydrazine derivative, or the carboxylate can be present in a stoichiometric amount about equal to that of the hydrazine derivative, or it could be said, in an amount at least as great as that of the hydrazine derivative.
  • the acid form of the carboxylate has the formula RCO 2 H wherein R is an organic group.
  • the acid for of the carboxylate has the. formula RCO 2 H wherein R is an aikyl group or a haloalkyl group.
  • the first pK a is preferably in the range of about -2 to about +7, more preferably in the range of about —1 to about +6, more preferably in the range of about 0 to about +5.
  • the first pK a can be about 0.3 first pK a , or it can be about 2.8, or the first pK a can be about 4.8.
  • the carboxylate can be one or more of acetate, trifluoroacetate, and monochloroacetate.
  • the acid is preferably an ammonium acid and the second pK a preferably exceeds the first pK a by at least 2.
  • the ammonium acid typically has the wherein each of R 1 ⁇ R 2 and R 3 is an organic group or hydrogen. Commonly, each of R ⁇ , R 2 and R 3 of the ammonium acid is an aikyl group (e.g., methyl, ethyl, propyl, butyl and pentyl) or hydrogen. In a specifically disclosed aspect of the invention, the acid having the second pK a is triethylammonium.
  • the anolyte solution includes a counterion to the carboxylate, the counterion having the formula R ⁇ R 4 N ⁇ wherein each of R l5 R 2 , R , and R 4 is an organic group selected from the group described in connection with R 1 ⁇ R 2 and R of R ! R 2 R 3 NH + .
  • the contacting step is preferably carried out in an anodic half cell divided from and operatively linked to a cathodic half cell.
  • the half cells are linked by an ion permselective diaphragm.
  • the diaphragm is preferably made up of a synthetic polymer having anions affixed (usually covalently bonded) thereto.
  • a preferred anion is perfluorosulfonate.
  • a commercially available diaphragm suitable for many aspects of the invention is that sold under the name Nafion.
  • compound II, V, or VII as the case may be, has a more positive potential than the voltage at which the contacting step is conducted.
  • Compound HI preferably has first and second peak potentials, each of which potentials is between about 0 and 3 volts against Ag/AgCl, more preferably between about 1 and 2 volts.
  • the mole ratio of the compound having formula III to the compound having formula II, V, or VII, as the case may be, is from about 1 : 1 to about 1000 : 1 ; more preferably between 500: 1 and 1:1; more preferably between about 100: and 1:1; more preferably between about 25:1 and 1:1; more preferably between about 10:1 and 1:1; more preferably between about 5 : 1 and 1:1, more preferably between about 2 : 1 and 1:1.
  • the process can be carried out such that the electric potential applied during the contacting step is applied for a period between about 1 minute and 10 hours.
  • the invention is a process of addition of a nitrogen across a multiple bond of an organic molecule wherein a first atom of the multiple bond is a carbon atom, and the second atom is selected from the group of carbon, oxygen and nitrogen, the improvement comprising electrochemically generating the nitrogen for the addition from a primary hydrazine derivative in the presence of a carboxylate anion.
  • the nitrogen is generated from a compound having the structure indicated by formula III, as defined above and that the organic molecule has the structure indicated by formula I formula VII.
  • Another process of the invention is addition of a nitrogen to a heteroatom of an organic molecule wherein the heteroatom forms a double bond with an oxygen atom and is a P, S, Se or Te atom, the improvement comprising electrochemically generating the nitrogen for the addition from a primary hydrazine derivative in the presence of a carboxylate anion.
  • the nitrogen is preferably generated from a compound having the structure indicated by formula III, as defined above and the organic molecule has the structure indicated by formula V.
  • Another aspect of the invention is a process for electrochemically generating a nitrene.
  • the process includes exposing a hydrazine derivative contained in an anolyte solution of an electroytic cell to the anode of the cell in the presence of a carboxylate ion, wherein one of the nitrogens of the hydrazine group is a primary amino group.
  • the anolyte solution is substantially free of a metal catalyst, particularly a toxic metal catalyst.
  • the anode a platinum electrode.
  • an acid form of the carboxylate has a first pK a
  • the anolyte solution further comprises an acid having a second pK a wherein the second pK a exceeds the first pK a
  • the carboxylate and acid (or counterion to the carboxylate) are selected as described above.
  • the carboxylate and the acid having the second pK a are solubilized in the solution and the carboxylate is provided in solution in a stoichiometric amount equal to at least half that of the hydrazine derivative, but more preferably to at least 60% that of the hydrazine derivative, or at least 70% that of the hydrazine derivative, or 80% that of the hydrazine derivative, or 90% that of the hydrazine derivative, or the carboxylate can be present in a stoichiometric amount about equal to that of the hydrazine derivative, or it could be said, in an amount at least as great as that of the hydrazine derivative.
  • the hydrazine derivative in this process for generating a nitrene, can be a molecule having the structure indicated as formula III as described above, and the anolyte solution can be a solvent as described above.
  • the invention is an apparatus for electrochemical generation of a nitrene.
  • the apparatus includes an anodic half cell operatively linked to a cathodic half cell, and an anolyte solution comprising a carboxylate anion and a primary hydrazine derivative.
  • the half cells are linked by an ion permselective diaphragm.
  • a preferred diaphragm is a synthetic polymer having anions affixed thereto, as by covalent bonding, and the anions can include perfluorosulfonate groups.
  • a commercially available diaphragm suitable for use according to many processes of the invention is a Nafion membrane.
  • the hydrazine of the apparatus includes any of those having formula III, as described above.
  • the anolyte solution is substantially free of a metal catalyst
  • the anode of the apparatus is a platinum electrode.
  • the an acid form of the carboxylate of the apparatus has a first pK a
  • the anolyte solution includes an acid having a second pK a wherein the second pK a exceeds the first pK a .
  • the carboxylate and counterion included in the apparatus can be selected and included in the apparatus as described above.
  • An apparatus of the invention can be used for nitrene generation, an aziridination, sulfoximation, or other nitrogen addition to a suitable organic substrate.
  • Another aspect of the invention is a process for screening an olefin for electrochemical aziridination of an olefin with a hydrazine derivative, the process comprising the steps of: providing the olefin; determining the redox potential of the olefin at a predetermined voltage at which the aziridine derivative is oxidized, wherein a said olefin determined to have a less positive potential than the predetermined voltage is eliminated as a candidate for electrochemical aziridination by the hydrazine derivative.
  • the invention is a process for screening an olefin for electrochemical aziridination of an olefin with a hydrazine derivative, the process comprising the steps of: providing the olefin; determining the redox potential of the olefin at a predetermined voltage at which the aziridine derivative is oxidized, wherein a said olefin determined to have a more positive potential than the predetermined voltage is selected as a candidate for electrochemical aziridination by the hydrazine derivative.
  • the hydrazine derivative has first and second peak potentials, each of which potentials is between about 0 and 3 volts against Ag/AgCl, more preferably between about 1 and
  • Figure 1 shows cyclic voltammetry (CV) of N-aminophthalimide (dashed line) and cyclohexene (solid line) in acetonitrile with 0.1 M HEt 3 ⁇ OAc on platinum electrode; j-axis: current, 10 "6 A, -axis: potential vs Ag/AgCl, V;
  • FIG. 2 shows Scheme 1, electrochemical aziridination of olefins
  • Figure 3 shows five olefins which did not undergo electrochemical aziridination
  • Figure 4 shows cyclic voltammetry of N-aminophthalimide (dashed line) and cyclohexene (solid line) in acetonitrile with 0.1 M HEt ⁇ OAc on glassy carbon electrode; ; ⁇ -axis: current, 10 "6 A, x-axis: potential vs Ag/AgCl, V;
  • Figure 5 shows cyclic voltammetry of N-aminophthalimide (dashed line) and tetramethylene sulfoxide (solid line) in acetonitrile with 0.1 M HEt 3 ⁇ OAc on platinum electrode; y-axis: current, 10 "6 A, x-axis: potential vs Ag/AgCl, V; Figure 6 shows cyclic voltammetry of N-aminophthalimide (dashed line) and tetramethylene sulfoxide (solid line) in acetonitrile with 0.1 M HEt 3 ⁇ OAc on glassy carbon electrode; .y-axis: current, 10 "6 A, ⁇ -axis: potential vs Ag/AgCl, V;
  • FIG. 7 shows Scheme 2, electrochemical sulfoximination;
  • Figure 8 shows Scheme 3, a proposed mechanism for Pb(OAc) 4 -mediated aziridination;
  • Figure 9 shows Scheme 4, a proposed mechanism for electrochemical oxidation of N-aminophthalimide.
  • DMSO was purchased from BDH Inc., Canada.
  • Anhydrous aluminum chloride was purchased from Anachemia Canada Inc.
  • Column chromatography was carried out using 230-400 mesh silica gel.
  • X H ⁇ MR spectra were referenced to residual CHC1 3 ( ⁇ 7.26 ppm) and 13 C spectra were referenced to CDC1 3 ( ⁇ 77.2 ppm).
  • Cyclic voltammetry characterization was conducted on a BAS CV-50W Voltammetric Analyzer (Bioanalytical Systems, Inc.) equipped with a BAS C3 three-electrode cell stand.
  • a three-compartment anodic: 2.0 cm dia. x 10 cm; cathodic: 2.0 cm dia. x 10 cm; reference: 1.0 cm dia.
  • N-aminophthalimide 7 Hydrazine monohydrate (4.4 g) in 95% ethanol (80 mL) was treated with powdered phthalimide (12 g) and the mixture was stirred at room temperature for 2 min. The resulting spongy mass was quickly heated and refluxed for 3 min. while ammonia was evolved. Cold water (250 mL) was added at once and N- aminophthalimide crystallized during an hour. Recrystallization from 95% ethanol gave white needles (5.6 g, 43%, Mp 223-224 °C). Electrochemical Aziridination of Cyclohexene
  • the anodic compartment was charged with 82 mg (1.0 mmol) cyclohexene, 210 mg (1.3 mmol) N-aminophthalimide, 60 mg (1.0 mmol) acetic acid (glacial), 101 mg (1.0 mmol) triethylamine, and 20 mL acetonitrile. Portions of 0.05 M AcOH in MeC ⁇ were added to the cathodic (20 mL) and reference (4 mL) compartments. Platinum foils (2.5 x 2.5 cm, 99.99%) were used as working and auxiliary electrodes. Silver wire (1.5 mm dia., 99.99%) was used as a pseudo-reference electrode.
  • the electrolysis was performed at +1.80 V (with an AMEL potentiostat, Model 2049) at ambient temperature and was stopped when the cell current dropped to less than 5% of its original value.
  • the contents of anodic compartment were collected and concentrated in vacuo.
  • the residue was washed with water and extracted with dichloromethane (3 x 5 mL).
  • the organic phases were combined, dried over MgSO , concentrated, charged onto a silica gel column, and eluted using EtOAc/hexane (1:3) which afforded 7-phthalimido-7- azabicyclo[4.1.0]heptane (1) as a yellow solid (223 mg, 85%).
  • 2-Cyanoethyl phenyl sulfoxide A modified literature procedure 14 was used to make this compound. Thiophenol (1.10 g, 10 mmol) was added dropwise to a mixture of acrylonitrile (1.06 g, 20 mmol) and tetrabutylammonium hydroxide (40 wt% aq. 0.1 mL) dissolved in dichloromethane (50 mL). The reaction mixture was stirred at room temperature for 2 hours and concentrated in vacuo.
  • 4-Methoxydiphenyl sulfoxide A modified literature procedure was used to prepare this compound. To a well stirred suspension of sodium benzenesulfinate (5.41 g, 30 mmol, dried at 100 °C for 2 h.) in cold (ice water bath) dry toluene (30 mL) was added dropwise thionyl chloride (2.98 g, 25 mmol). The reaction mixture was allowed to warm up to room temperature and stirred overnight.
  • Toluene was removed by applying high vacuum (0.5 mmHg) and crude bezenesulfinyl chloride was dissolved in dry DCM (20 mL), cooled to 0-5 °C, and was added dropwise to a mixture of anisole (3.24 g, 30 mmol) and anhydrous aluminum chloride (4.0 g, 30 mmol) in DCM (20 mL) at 0-5 °C under nitrogen. This mixture was stirred at 0-5 °C for 3 hours. Water was added slowly and organic phase separated, dried over MgSO 4 , filtered and concentrated in vacuo to give a pale yellow oil.
  • sulfoxide substrate corresponding to each sulfoximine listed in Table 2, the following procedure was followed.
  • the anodic compartment was charged with 1.0 mmol sulfoxide, 210 mg (1.3 mmol) N-aminophthalimide, 78 mg (1.3 mmol) acetic acid (glacial), 130 mg (1.3 mmol) triethylamine, and 20 mL acetonitrile.
  • Portions of 0.05 M AcOH in MeC ⁇ were added to the cathodic (20 mL) and reference (4 mL) compartments.
  • Platinum foils 2.5 x 2.5 cm, 99.99%) were used as working and auxiliary electrodes.
  • Silver wire 1.5 mm dia., 99.99%) was used as a pseudo-reference electrode.
  • the electrolysis was performed at +1.80 V at ambient temperature and was stopped when the cell current dropped to less than 5% of its original value.
  • the contents of anodic compartment were collected and concentrated in vacuo.
  • the residue was washed with water and extracted with dichloromethane (3 x 5 mL).
  • the organic phases were combined, dried over MgSO 4 , concentrated, charged onto a silica gel column, and eluted using EtOAc/hexane to afford sulfoximine.
  • the isolated products were characterized, as indicated below.
  • N-Phthalimido-S,S-dimethylsulfoximine (ll): ⁇ 9 1H ⁇ MR (CDC1 3 ) ⁇ : 3.29 (s, 6H), 7.67-7.71 (m, 2H), 7.79-7.82 (m, 2H). 13 C NMR (CDC1 3 ) ⁇ : 41.39, 123.38, 130.74, 134.15, 167.44. Mp 205-206 °C (lit. 20 208-210 °C).
  • Mp 138-140 °C (lit. 20 136-137 °C).
  • tetramethylene sulfoxide (0.01 M in acetonitrile) produces a considerably smaller anodic current of -7.52 ⁇ A than the current observed for N-aminophthalimide (-152 ⁇ A), suggesting a relatively kinetically sluggish background oxidation of sulfoxides on a platinum electrode.
  • the N-acetoxyamino intermediate dimerizes to generate the tetrazene which then decomposes to phthalimide by extrusion of ⁇ 2 .
  • Fuchigami and coworkers 27 have shown that the electrochemical oxidation of N-aminophthalimide using Bii ⁇ BF/i or LiClO 4 as supporting electrolyte at 0 °C gave tetrazene as major product and 10 - 20% of phthalimide.
  • the authors proposed an electrochemically generated N-nitrene intermediate which inserts into the ⁇ -H ⁇ -bond of the unoxidized N-aminophthalimide to afford the tetrazane intermediate (Scheme 4 of Figure 9).
  • the tetrazane is further oxidized to give tetrazene.
  • the continuum of accessible electrode potentials provided by electrochemistry enables differentiating substrates based on their overpotentials.

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Abstract

L'invention concerne un procédé et un appareil destinés à ajouter de l'azote à une molécule organique dans des conditions électrochimiques. Ces procédés comprennent l'aziridination d'oléfines et l'imination de sulfoxyde en vue de former des sulfoxymines. L'invention concerne également la production de nitrène en présence d'un carboxylate.
PCT/CA2002/001163 2001-07-25 2002-07-25 Transfert d'atomes d'azote WO2003010361A2 (fr)

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US8497252B2 (en) 2008-06-09 2013-07-30 New York Medical College Compositions comprising cardiac stem cells overexpressing specific microRNAs and methods of their use in repairing damaged myocardium
CN114875434A (zh) * 2022-04-12 2022-08-09 齐鲁工业大学 一种亚胺类化合物胺化的电化学方法

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CN108677210B (zh) * 2018-04-17 2019-10-29 大连理工大学 一种酮与羧酸在电化学氢泵反应器中一步加氢酯化的方法
CN119194469B (zh) * 2024-11-28 2025-02-25 山东金科力电源科技有限公司 一种电化学合成胺类化合物的方法

Non-Patent Citations (2)

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Title
T. SIU, A..K. YUDIN: "Electrochemical Imination of Sulfoxides Using N-Aminophthalimide" ORG. LETT., vol. 4, no. 11, 5 January 2002 (2002-01-05), pages 1839-1842, XP002243494 *
T. SIU, A.K. YUDIN: "Practical Olefin Aziridation with a Broad Substrate Scope" J. AM. CHEM. SOC., vol. 124, no. 4, 5 January 2002 (2002-01-05), pages 530-531, XP002243493 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8497252B2 (en) 2008-06-09 2013-07-30 New York Medical College Compositions comprising cardiac stem cells overexpressing specific microRNAs and methods of their use in repairing damaged myocardium
CN114875434A (zh) * 2022-04-12 2022-08-09 齐鲁工业大学 一种亚胺类化合物胺化的电化学方法
CN114875434B (zh) * 2022-04-12 2023-08-11 齐鲁工业大学 一种亚胺类化合物胺化的电化学方法

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