EP2139853A1 - Verfahren zur herstellung von carbenvorläufern des caac-typs und ihre verwendung zur herstellung besagter carbene - Google Patents

Verfahren zur herstellung von carbenvorläufern des caac-typs und ihre verwendung zur herstellung besagter carbene

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Publication number
EP2139853A1
EP2139853A1 EP08736019A EP08736019A EP2139853A1 EP 2139853 A1 EP2139853 A1 EP 2139853A1 EP 08736019 A EP08736019 A EP 08736019A EP 08736019 A EP08736019 A EP 08736019A EP 2139853 A1 EP2139853 A1 EP 2139853A1
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group
formula
represent
aryl
alkyl
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French (fr)
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Gérard Mignani
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Rhodia Operations SAS
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Rhodia Operations SAS
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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
    • C07D209/54—Spiro-condensed
    • 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
    • C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
    • C07D207/06—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 no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms

Definitions

  • the subject of the present invention is a process for the preparation of carbene precursors of the CAAC (Cyclic) (Alkyl) (Amino) (Carbenes) type and their use for preparing said carbenes.
  • the invention relates to the use of novel synthetic intermediates for preparing carbene precursors of CAAC type.
  • the carbenes are compounds that can be used as organocatalysts or as metal ligands such as palladium, platinum, nickel, ruthenium, rhodium, iridium, copper and iron thus forming stable organometallic complexes which can be used as catalysts for organic reactions, especially in the coupling reactions between an electrophilic reagent, most often an aromatic compound carrying a leaving group (such as halogen, sulphonic ester, azonium, etc.) and a nucleophilic compound providing a a carbon atom or a heteroatom capable of substituting for the leaving group, thus creating a CC or C-HE bond (HE being a heteroatom for example N 1 O, S, Si ).
  • a leaving group such as halogen, sulphonic ester, azonium, etc.
  • CAACs alkylaminocyclic carbene
  • Cyclic (Alkyl) (Amino) Carbenes are known compounds and described in the literature in particular in WO 2006/138166.
  • a synthesis route of said carbene is represented by the following reaction scheme: TfOTf
  • the Applicant proposes a method to avoid this disadvantage by involving a different intermediate product.
  • the subject of the present invention is the use, as intermediate for the production of a CAAC carbene precursor, of a compound corresponding to the following formula:
  • w is equal to 1 or 2
  • R 1, R 2 which may be identical or different, represent an alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, alkoxy, alkenyloxy, alkynyloxy, aryloxy or alkoxycarbonyl group,
  • R 1 and R 2 can be bonded together to form a spirocycle comprising from 3 to 18 atoms
  • R'1, R ' 2 , R'3, R'4, R'5, identical or different, represent a hydrogen atom, an alkyl group, cycloalkyl, aryl, aralkyl.
  • alkyl is understood to mean a linear or branched hydrocarbon chain containing from 1 to 15 carbon atoms, preferably from more preferably in CrC 4 .
  • alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl and t-butyl.
  • alkoxy is meant an alkyl-O- group in which the term alkyl has the meaning given above.
  • Preferred examples of alkoxy groups are methoxy or ethoxy.
  • alkoxycarbonyl is meant the alkoxy-C (O) - group in which the alkoxy group has the definition given above.
  • alkenyl means a straight or branched hydrocarbon chain having one double bond, C2-C8, preferably C2-C6 and most preferably C2-C4.
  • alkenyl groups include vinyl, 1-propenyl, 2-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl and isobutenyl.
  • alkynyl is meant a linear or branched hydrocarbon chain comprising a C 2 -C 8 , preferably C 2 -C 6 and even more preferentially C 2 -C 4, triple bond.
  • alkynyl groups include ethynyl, 1-propynyl, 1-butynyl, 2-butynyl.
  • alkenyloxy and alkynyloxy are meant respectively an alkenyl-O- and alkynyl-O- group in which the terms alkenyl and alkynyl have the meanings given above.
  • cycloalkyl is meant a cyclic hydrocarbon group, monocyclic C3-C10 preferably a cyclopentyl or cyclohexyl or polycyclic (bicyclic or tricyclic) C 4 -C 8 , in particular adamantyl or norbornyl.
  • cycloalkane spirocycle is meant as previously defined, a mono- or polycyclic structure, C 8 -C 18, preferably C 3 -C 3
  • aryl is meant an aromatic mono- or polycyclic group, preferably mono- or bicyclic C 6 -C 20 , preferably phenyl or naphthyl.
  • the group is polycyclic, that is to say that it comprises more than one ring nucleus, the ring nuclei can be condensed two by two or attached in pairs by bonds ⁇ .
  • groups (C 6 -C 8) aryl include phenyl, naphthyl.
  • aryloxy is meant an aryl-O- group in which the aryl group has the meaning given above.
  • arylalkyl is meant a hydrocarbon group, linear or branched bearer of a monocyclic aromatic ring C 7 -C 2, preferably benzyl: the aliphatic chain contains 1 or 2 carbon atoms It should be noted that since one of the groups R 1, R 2, R '1, R' 2, R '3, R' 4, R '5 comprises a ring, this ring may be substituted by one or more preferably two or three substituents. The nature of the substituent can be any since it does not interfere at the level of the CAAC synthesis.
  • substituents represented by R 1 include alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, amino, amino groups substituted by alkyl, cycloalkyl groups; a nitrile group; a halogen atom, preferably chlorine or fluorine; a haloalkyl group, preferably perfluoromethyl.
  • the compounds of formula (I) are referred to as "intermediate compounds" because they are intermediates for the production of carbene precursors.
  • the preferred intermediate compounds have the formula (Ia) or (Ib):
  • R 1, R 2 which may be identical or different, represent an alkyl group, an optionally substituted aryl group, preferably an optionally substituted phenyl or naphthyl group,
  • R 1 and R 2 are bonded together to form a spirocyclic ring of cycloalkane, mono- or polycyclic type
  • R ' 3 , R 4 , R' 5 which may be identical or different, represent an alkyl group
  • R 4 , R ' 5 also represent a hydrogen atom.
  • R 1, R 2 represent an optionally substituted aryl group;
  • the substituent (s) may be as previously defined (R t ) but are preferably alkyl groups and / or alkoxy groups and / or aryl groups, preferably phenyl.
  • the intermediate compounds prepared more preferably correspond to formula (Ia) or (Ib) in which:
  • R 1, R 2 which may be identical or different, represent a linear or branched alkyl group having from 1 to 4 carbon atoms or a phenyl group, a substituted phenyl group,
  • R 1 and R 2 are linked together to form a cyclopentane, a cyclohexane or a norbornane,
  • R'3, R ' 4 , R' 5 identical or different, represent a linear or branched alkyl group having 1 to 4 carbon atoms and R ' 4 , R' 5 also represent a hydrogen atom.
  • Another subject of the invention lies in the process for the preparation of a carbene precursor CAAC, also called "iminium salt" of formula
  • R represents an alkyl, cycloalkyl, aryl, aralkyl or heteroaryl group
  • R 1, R 2 which may be identical or different, represent an alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, alkoxy, alkenyloxy, alkynyloxy, aryloxy or alkoxycarbonyl group,
  • R 1 and R 2 can be bonded together to form a spirocycle comprising from 3 to 18 atoms
  • A represents a ring comprising 5 or 6 atoms of which at least one of the atoms is a nitrogen atom as represented,
  • L is a divalent group corresponding to the following formula:
  • w is a number equal to 1 or 2
  • R'1, R ' 2 , R'3, R'4, R'5, identical or different, represent a hydrogen atom, an alkyl group, cycloalkyl, aryl, aralkyl,
  • Z is an anion, characterized in that it comprises at least one reaction step of: - the compound of formula (I):
  • R1, R2, R'1, R'2, R'3, R'4, R'5 and w have the meaning given above,
  • R represents an alkyl, cycloalkyl, aryl, aralkyl or heteroaryl group
  • R, R 1, R 2 , R ' 1 , R' 2 , R 's, R' 4 , R 's and w have the meaning given above.
  • the intermediate compound of formula (I) is prepared by reaction of an aldehyde having at least one hydrogen atom in position ⁇ with respect to the carbonyl group and an unsaturated reagent, a leaving group, in bi-phasic medium, in the presence of a strong base and a phase transfer catalyst.
  • Another object of the invention resides in the process for preparing a CAAC carbene precursor of formula (VI) according to a cyclization step of the compound of formula (IV).
  • the preparation of the intermediate compound of formula (I) is carried out according to a preparation process which comprises the reaction of an aldehyde having at least one hydrogen atom in position ⁇ with respect to the carbonyl group and an unsaturated reagent bearing a leaving group in a bi-phasic medium in the presence of a strong base and a phase transfer catalyst.
  • R 1, R 2 which may be identical or different, represent an alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, alkoxy, alkenyloxy, alkynyloxy, aryloxy or alkoxycarbonyl group,
  • R 1 and R 2 may be bonded together to form a spirocycle comprising from 3 to 18 atoms, and an unsaturated reagent carrying a leaving group:
  • - w is a number equal to 1 or 2
  • R ', R'2, R'3, R 4, R' 5, identical or different, represent a hydrogen atom, alkyl, cycloalkyl, aryl, aralkyl,
  • Y represents a leaving group
  • Y represents a leaving group selected from bromine, chlorine or a sulphonic ester group of formula - OSO 2 - R e , in which R e is a hydrocarbon group.
  • R e is a hydrocarbon group of any kind.
  • Y is a leaving group, it is interesting from an economic point of view that R e is of a simple nature, and more particularly represents a linear or branched alkyl group having from 1 to 4 carbon atoms, preferably, a methyl or ethyl group but it may also represent for example a phenyl or tolyl group or a trifluoromethyl group.
  • the preferred group is a triflate group which corresponds to a group R e representing a trifluoromethyl group.
  • a chlorine atom is preferably selected.
  • the amount of unsaturated reagent of formula (III) to be used expressed relative to the amount of the aldehyde of formula (II) is at least equal to the stoichiometry.
  • the ratio between the number of unsaturated reactive moles of formula (III) and the number of moles of aldehyde of formula (II) varies between 1 and 1.5, and is preferably between 1, 2 and 1.3. .
  • a base which can be inorganic or organic.
  • the base used must be strong enough to allow the anionization of the carbon - hydrogen bond of the aldehyde.
  • strong base is meant a base whose pka of the conjugated acid is greater than or equal to 9, preferably between 10 and 14.
  • PKa is defined as the ionic dissociation constant of the acid / base pair, when water is used as the solvent.
  • a base having a pKa as defined by the invention reference may be made, inter alia, to the HANDBOOK OF CHEMISTRY AND PHYSICS, 66 th edition, p. D-161 AND D-162.
  • a mineral base such as an alkali or alkaline earth metal hydroxide, preferably sodium hydroxide, potassium hydroxide or lithium hydroxide; an alkali metal phosphate or hydrogenphosphate, preferably sodium or potassium phosphate or an organic base, preferably sodium methoxide.
  • quaternary ammonium hydroxide preference is given to the use of tetraalkylammonium or trialkylbenzylammonium hydroxides, the identical or different alkyl groups of which represent a linear or branched alkyl chain having from 1 to 12 carbon atoms, from preferably 1 to 6 carbon atoms.
  • Tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetrabutylammonium hydroxide or trimethylbenzylammonium hydroxide are preferably chosen.
  • the base is used, indifferently in the form of a powder or in the form of an aqueous solution.
  • the concentration of the basic starting solution is not critical.
  • the alkali metal hydroxide solution used has a concentration generally of between 10 and 50% by weight.
  • the amount of base used expressed by the ratio between the number of moles of OH ' ions and the number of moles of compound of formula (II) varies between 2 and 5, preferably between 3 and 4.
  • reaction of the compounds of formulas (II) and (III) is conducted in the absence or in the presence of an organic solvent.
  • the organic solvent is chosen such that it is inert under the reaction conditions of the invention.
  • aromatic hydrocarbons such as toluene, xylenes, cumene, mesitylene, petroleum fractions consisting of a mixture of alkylbenzenes, in particular Solvesso type cuts, and decalin.
  • the amount of solvent used is determined in such a way that the concentration of the compound of formula (II) in the organic solvent is preferably between 2 and 10 mol / liter, preferably around 3 mol / liter.
  • phase transfer catalyst a catalyst capable of passing the anion from the aqueous phase to the organic phase.
  • phase transfer catalysts in particular, those described in the book by Jerry March - Advanced Organic Chemistry, 4th Edition, John Wiley & Sons, 1992 p. 362 and following.
  • the onium salts that can be used in the process of the invention are those whose onium ions derive in particular from nitrogen, phosphorus, sulfur, oxygen, carbon or iodine and coordinated to hydrocarbon residues.
  • hydrocarbon residues coordinated to these various elements are optionally substituted alkyl, alkenyl, aryl, cycloalkyl or aralkyl groups, two coordinated hydrocarbon radicals which can together form a single divalent group.
  • onium ions which can be used in the present process of the invention, those having the following general formula are particularly suitable: X 1 ⁇ / X 2
  • Z 1 represents N or P
  • X 1 , X 2 , X 3 , X 4 which are identical or different, represent: an alkyl group, linear or branched, having 1 to 16 carbon atoms and optionally substituted by one or more groups or atoms phenyl, hydroxyl, halogen, nitro, alkoxy or alkoxycarbonyl, alkoxy groups having 1 to 4 carbon atoms,. a linear or branched alkenyl group having 2 to 12 carbon atoms,
  • an aryl group having 6 to 10 carbon atoms optionally substituted by one or more alkyl groups or atoms having 1 to 4 carbon atoms, alkoxy, alkoxycarbonyl, the alkoxy group having 1 to 4 carbon atoms, or halogen,
  • two of said groups X 1 to X 4 may together form a linear or branched alkylene, alkenylene or alkadienylene group having from 3 to 6 carbon atoms.
  • said anions may be chosen from PO 4 3 -, HPO 4 2 “ , H 2 PO 4 “ , CH 3 SO 3 “ , Ph-SO 3 “ , NO 3 “ , SO 4 2 “ , PF 6 “ , CI “ , Br “ , I “ , Ph having the above meaning.
  • the quaternary ammonium ions the quaternary phosphonium ions, will most often be preferred.
  • Ammonium or phosphonium ions whose four groups are alkyl groups having from 1 to 5 carbon atoms or a benzyl group are particularly particularly suitable.
  • the anion Br “ , CI “ , OH “ , HSO 4 " will be preferred.
  • Catalysts very well suited to the present invention are thbutylbenzylammonium or phosphonium chloride or bromide, tetramethylammonium or phosphonium chloride or bromide, chloride or tetraethylammonium bromide or phosphonium bromide, tetrabutylammonium chloride or bromide or phosphonium.
  • Benzyltributlylammonium chloride or bromide is particularly preferred, the chlorinated derivative being more particularly preferred.
  • the onium salt may be introduced during the process of the invention, in the solid state or in the form of a solution in one of its solvents, most often water.
  • phase transfer catalysts that may be used in the process of the invention include tri (ether-amines), especially those described in FR-A-2,455,570, which have the following formula:
  • R 3 represents an alkyl group having 1 to 24 carbon atoms, a cyclohexyl group, a phenyl group, an alkylphenyl group containing from 7 to 12 carbon atoms,
  • a and B which are identical or different, represent a linear alkanediyl group containing 2 or 3 carbon atoms optionally substituted by a methyl or ethyl group, n is an integer between 0 and 4.
  • catalysts of formula (F 2 ) there may be mentioned ths (dioxa-3,6-heptyl) amine sold under the name TDA-1.
  • a preferred embodiment comprises the parallel introduction of the compounds of formula (II) and (III) in a medium comprising the solvent (water and / or organic solvent), the base and the phase transfer catalyst.
  • the introduction of the compounds of formulas (II) and (III) is advantageously carried out progressively, fractionally or continuously.
  • the duration of addition is for example between 2 and 10 hours, preferably between 4 and 5 hours.
  • the coupling reaction between the compounds of formula (II) and (III) is generally carried out at a temperature ranging between 50 ° C. and 100 ° C., preferably between 70 ° and 80 ° C.
  • the process of the invention is carried out under atmospheric pressure but preferably under a controlled atmosphere of inert gases such as nitrogen or rare gases, for example argon. A pressure slightly above or below atmospheric pressure may be suitable.
  • R1, R2, R'1, R'2, R'3, R'4, R'5 and w have the meaning given above.
  • the said compound is recovered from the reaction medium which comprises an organic phase comprising the addition product of formula (I) and the reagents (II) or (III) in excess and an aqueous phase comprising the salts resulting from the reaction.
  • the organic and aqueous phases are separated.
  • the aqueous phase can be washed once or twice with the aid of an organic solvent, preferably the solvent chosen for the reaction.
  • the organic phases are combined and then a usual drying operation is preferably carried out on desiccant, for example sodium or magnesium sulphate.
  • desiccant for example sodium or magnesium sulphate.
  • the reaction medium is generally concentrated by evaporation and then the intermediate compound of formula (I) is recovered in a conventional manner, preferably by distillation.
  • R1, R2, R'1, R'2, R'3, R'4, R'5 and w have the meaning given above,
  • R represents an alkyl, cycloalkyl, aryl, aralkyl or heteroaryl group, characterized in that it is obtained by reaction in the presence of a strong acid, of the compound of formula (I) with a primary amine of formula (V) :
  • R represents an alkyl, cycloalkyl, aryl, aralkyl or heteroaryl group.
  • heteroaryl is meant an aryl group as defined above, one to three carbon atoms may be replaced by a heteroatom, preferably oxygen or nitrogen.
  • the group R is a preferred hydrocarbon group which is sterically hindered.
  • the substituents on the phenyl group are preferably in the ortho and / or para and / or ortho position relative to the amino group.
  • the substituents on the naphthyl group are preferably in the ortho and / or ortho position relative to the amino group.
  • reaction of the compound of formula (I) and of the primary amine of formula (V) can be carried out according to a basic catalysis that is to say without catalyst when the amine is sufficiently basic, that is to say that his pka in the water is greater than or equal to 10.
  • reaction of the compound of formula (I) and the primary amine of formula (V) may also be catalyzed by an acid.
  • the reaction is carried out in the presence of a catalytic amount of a strong protonic acid, that is to say an acid having a pKa in water of less than 5, preferably less than 1.
  • strong protic acids include, inter alia, sulfuric acid, chlorosulfuric acid, perchloric acid; sulphonic acids such as, for example, methanesulphonic acid, trifluoromethanesulphonic acid, toluenesulphonic acid, phenolsulphonic acid; carboxylic acids such as acetic acid, trifluoroacetic acid.
  • protic acid catalysts include sulfonic resins and more particularly resins marketed under different commercial names.
  • the following resins can be mentioned, among others: TEMEX 50, AMBERLYST 15, AMBERLYST 35, AMBERLYST 36,
  • the above resins consist of a polystyrene backbone which carries functional groups which are sulfonic groups.
  • the polystyrene backbone is obtained by polymerization of styrene and divinylbenzene, under the influence of an activation catalyst, most often an organic peroxide, which leads to a cross-linked polystyrene which is then treated with sulfuric acid or concentrated sulphochloride resulting in a sulfonated styrene-divinylbenzene copolymer.
  • sulphonic resins which are phenol-formaldehyde copolymers and which relate to the aromatic ring a methylenesulphonic group, for example the resin marketed under the name DUOLITE ARC 9359.
  • resins available on the market are also suitable and mention may be made of perfluorinated resins bearing sulphonic groups and, more particularly, NAFION, which is a copolymer of tetrafluoroethylene and of perfluoro [2- (fluorosulfonylethoxy) propyl] vinyl ether.
  • NAFION is a copolymer of tetrafluoroethylene and of perfluoro [2- (fluorosulfonylethoxy) propyl] vinyl ether.
  • methanesulfonic acid or p-toluenesulfonic acid is preferably used.
  • the amount of acid used is preferably catalytic.
  • the amount of acid expressed relative to the amount of aldehyde represents from 1 to 10% by weight, preferably from 1 to 5% by weight of aldehyde when the latter is defective in relation to the amine of formula (V).
  • the reaction is conducted in the presence of an organic solvent or not.
  • organic solvents examples include, in particular, aliphatic, cycloaliphatic, aromatic, halogenated or non-halogenated hydrocarbons, and more particularly hexane, heptane, isooctane, decane, benzene and toluene. , methylene chloride, chloroform.
  • the amount of solvent used is such that the concentration of the compound of formula (I) varies between 5 and 50% by weight of the reaction mixture.
  • the strong acid is brought into the presence of the mixture of the compound of formula (I) and the amine of formula (V) in the organic solvent.
  • the reaction mixture is subjected to azeotropic distillation.
  • the distillation is carried out at a temperature of between 40 ° C. and 120 ° C., at atmospheric pressure or under reduced pressure ranging from 10 mm of mercury to atmospheric pressure, preferably of between 10 and 200 mm. mercury.
  • R, R 1, R 2, R '1, R' 2, R '3, R' 4, R '5 and w have the meaning given above.
  • the imine is recovered by evaporation of the solvent, in particular by distillation under reduced pressure, for example between 1 and 100 mm of mercury.
  • Another alternative embodiment of the invention consists in eliminating the water formed in the reaction with the aid of a dehydrating agent, for example magnesium sulphate or a 4A aluminosilicate molecular sieve.
  • a dehydrating agent for example magnesium sulphate or a 4A aluminosilicate molecular sieve.
  • the invention also relates to the use of the imine compound of formula (IV) for the preparation of a cyclic iminium salt having the general formula (VI):
  • A represents a ring comprising 5 or 6 atoms of which at least one of the atoms is a nitrogen atom as represented,
  • L is a divalent group corresponding to the following formula:
  • w is a number equal to 1 or 2
  • R ' 2 , R'3, R'4, R'5, identical or different, represent a hydrogen atom, an alkyl group, cycloalkyl, aryl, aralkyl,
  • R, R 1, R 2 have the meaning given above
  • Z represents an anion such as, for example, a halide, preferably a chloride (in the form of CI “ , HCl 2 " or a mixture thereof) or a bromide, an acetate, trifluoroacetate, mesylate or tosylate group.
  • a halide preferably a chloride (in the form of CI " , HCl 2 " or a mixture thereof) or a bromide, an acetate, trifluoroacetate, mesylate or tosylate group.
  • the compound of formula (VI) is prepared from the linear iminium salt obtained by reaction of the compound of formula (IV) and a strong acid and then cyclization of the linear iminium salt obtained.
  • a strong acid is used.
  • strong protonic acids there may be mentioned more particularly hydracids such as hydrochloric acid, hydrobromic acid; halogenated or non-halogenated oxyacids such as sulfuric acid, perchloric acid; halogenated or unsaturated sulphonic acids such as fluorosulphonic acid, chlorosulphonic acid or trifluoromethanesulphonic acid, methanesulphonic acid, ethanesulphonic acid, ethanedisulphonic acid, benzenesulphonic acid, benzenedisulphonic acids, toluenesulphonic acids xylenesulphonic acids, naphthalenesulphonic acids and naphthalenesulphonic acids; halocarboxylic acids such as in particular trichloroacetic acid.
  • hydrochloric acid is preferably used.
  • Concentrated solutions of acid are preferably used because the presence of water in the medium slows the reaction kinetics.
  • a solution of hydrochloric acid at 37% by weight at a sulfuric acid solution of at least 95%, preferably greater than 98%.
  • hydrochloric acid is used in gaseous form.
  • the amount of acid expressed as the ratio of the number of proton equivalents to the number of moles of compound of formula (IV) may vary from about 1 to about 10, and preferably from 2 to 3.
  • the process of the invention is generally carried out under atmospheric pressure, but preferably under a controlled atmosphere of inert gases. It is possible to establish an atmosphere of rare gases, preferably argon, but it is more economical to use nitrogen.
  • the compound of formula (IV) and an organic solvent are charged, and then the acid is introduced, preferably bubbling with hydrochloric acid.
  • the temperature of the reaction is advantageously between about
  • the addition of the acid is in a progressive manner, continuously or in fractions for a period preferably varying between 3 and 8 hours.
  • reaction medium is brought to a reaction temperature preferably chosen between 60 ° C. and 100 ° C., and more preferably between 70 ° C. and 90 ° C.
  • R, R 1, R 2, Z, A and L have the meaning given above.
  • Z is preferably a chloride (as CI “ , HCI 2 " or a mixture thereof).
  • the carbene is generated from the cyclic iminium salt of formula (VI) by reacting the latter with a strong base.
  • butyllithium sodium tert-butylate or potassium
  • sodium amide sodium hydride
  • the strong base may be in liquid or solid form, preferably in solid form.
  • the amount of base expressed relative to the cyclic iminium salt of formula (VI) generally varies from the stoichiometric amount up to an excess of up to 200%.
  • the reaction is carried out at low temperature between -78 ° C and 25 ° C.
  • the reaction is conducted generally under atmospheric pressure but preferably under a controlled atmosphere of inert gases. It is possible to establish an atmosphere of rare gases, preferably argon, but it is more economical to use nitrogen.
  • the reaction is conducted under anhydrous conditions and in an aprotic organic solvent which is polar or non polar, selected inert under the conditions of the reaction.
  • the organic solvent contain less than 5 ppm water.
  • organic solvents mention may be made, inter alia, of aliphatic, cycloaliphatic or aromatic hydrocarbons and more particularly hexane, heptane, isooctane, decane, benzene, toluene; ether type solvents and especially diethyl ether, tetrahydrofuran, methyltetrahydrofuran.
  • the amount of organic solvent used is such that the concentration of the cyclic iminium salt of formula (VI) varies between 10 and 50% of the weight of the reaction medium.
  • the base is introduced into the organic solvent comprising the cyclic iminium salt of formula (VI).
  • the carbene is recovered in a conventional manner from the reaction medium.
  • the salts formed precipitate and are separated for example by filtration.
  • the solvent is more polar, such as THF, it is possible to precipitate the salts formed by adding a non-polar solvent such as toluene.
  • the carbene is found in the organic solvent and is recovered after evaporation of the solvent.
  • the process of the invention thus makes it possible to prepare carbenes of the type
  • CAACs that can be represented by the following formula:
  • - R, R 1, R 2 have the meaning given above, - A represents a ring comprising 5 or 6 atoms, at least one of the atoms is a nitrogen atom as shown,
  • L is a divalent group corresponding to the following formula:
  • R'1, R'2, R'3, R ' 4 , R'5 and w have the meaning given above, - (x) and (y) respectively locate the two bonds established between the carbon atom bearing groups R 1 and R 2 and the nitrogen atom carrying the group R.
  • CAAC carbenes prepared preferentially according to the process of the invention correspond to the formula (VII) in which A represents a ring of 5 or 6 atoms and L represents a divalent group comprising 2 or 3 atoms.
  • R, R 1, R 2 have the meaning given for formula (I),
  • R ' 3 , R 4 , R'5, identical or different, represent a hydrogen atom, an alkyl group, cycloalkyl, aryl, aralkyl.
  • Even more preferred carbenes have the formula (VIIa) or (VIIb) wherein R is an alkyl group, an optionally substituted aryl group, preferably an optionally substituted phenyl group; R 1, R 2 , which may be identical or different, represent an alkyl group, an optionally substituted aryl group, preferably an optionally substituted phenyl group or R 1 and R 2 are linked together to form a cycloalkane; R'3, R 4 , R ' 5, which may be identical or different, represent an alkyl group and R 4 and R' 5 also represent a hydrogen atom.
  • the process of the invention is quite suitable for preparing CAAC carbenes which have the formula (VIIa) or (VIIb) in which: - R represents a tert-butyl group, a phenyl group, a phenyl group substituted by a with three alkyl groups having from 1 to 4 carbon atoms,
  • R 1, R 2 which may be identical or different, represent a linear or branched alkyl group having from 1 to 4 carbon atoms or a phenyl group, or R 1 and R 2 are linked together to form a cyclopentane, a cyclohexane or a norbornane,
  • R'3, R ' 4 , R' 5 identical or different, represent a linear or branched alkyl group having 1 to 4 carbon atoms and R ' 4 , R' 5 also represent a hydrogen atom.
  • R' 4 , R' 5 also represent a hydrogen atom. Examples of preferred carbenes are given below:
  • Another object of the invention is, as new products, intermediates, imines precursors of iminium salt corresponding to the following formula:
  • R represents a branched alkyl group, an aryl group, a substituted aryl group,
  • R 1, R 2 which may be identical or different, represent an optionally substituted alkyl or aryl group
  • R 1 and R 2 can be bonded together to form a spirocycle comprising from 3 to 18 atoms
  • - R ' 3 represent a hydrogen atom, an alkyl group, an aryl group, a substituted aryl group, - R 4 , R' 5 , which may be identical or different, represent a hydrogen atom, an alkyl group or an aryl group; a substituted aryl group.
  • the aryl group is a phenyl or naphthyl group and the substituted aryl group is a phenyl or naphthyl group substituted by one or more alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, amino, amino groups. substituted with alkyl, cycloalkyl groups; a nitrile group; a halogen atom, preferably chlorine or fluorine; a haloalkyl group, preferably perfluoromethyl.
  • R represents a tert-butyl group; a phenyl group substituted with 3 methyl or ethyl groups in o, o 'and p positions; a phenyl group substituted with 2 isopropyl or tert-butyl groups in o and o 'position; a phenyl group substituted with 3 isopropyl or tert-butyl groups at o, o 'and p, R 1, R 2, which are identical or different, represent a methyl, ethyl, propyl, isopropyl, phenyl or substituted phenyl group;
  • R 1 and R 2 may be bonded together to form a spirocycle comprising from 3 to 10 atoms, R '3 represents a methyl group,
  • R 4 , R ' 5 identical or different, represent a hydrogen atom, a methyl group.
  • the preferred imines according to the invention correspond to the formula (IVa), in which at least one of the groups R 1, R 2 represent an optionally substituted aryl group, preferably an optionally substituted phenyl group.
  • the group R represents an optionally substituted aryl group, preferably an optionally substituted phenyl group.
  • the invention relates more particularly to imines corresponding to formula (IVa) in which: - R represents a phenyl group substituted by 2 isopropyl groups in the o and o 'position; a phenyl group substituted with 3 methyl or isopropyl groups at o, o 'and p,
  • R 1, R 2 identical or different, represent a methyl group, a phenyl group, a substituted phenyl group, or R 1 and R 2 may be bonded together to form a spirocycle comprising from 3 to 10 atoms,
  • R 4 , R ' 5 represent a hydrogen atom.
  • R s which are identical or different, represent a substituent chosen from alkyl or alkoxy groups having from 1 to 4 carbon atoms, m is the number of substituents equal to 1, 2 or 3, preferably 2 or 3,
  • R 1 represent one or more substituents having the meaning given above
  • R 4 , R ' 5 represent a hydrogen atom.
  • the invention also aims, as new products, the iminium salts, precursors of carbenes, corresponding to the following formula:
  • Z represents an anion preferably, a halide, chloride (in the form CI " , HCl 2 " or their mixture) or bromide; an acetate group; a trifluoroacetate group; a mesylate group; a tosylate group,
  • R represents a branched alkyl group, an aryl group, a substituted aryl group,
  • R 1, R 2 identical or different, represent an alkyl group, an aryl group, a substituted aryl group,
  • R 1 and R 2 may be bonded together to form a spirocycle comprising from 3 to 18 atoms, - R ' 3 represent a hydrogen atom, an alkyl group, an aryl group, a substituted aryl group,
  • R 4 , R ' 5 identical or different, represent a hydrogen atom, an alkyl group, an aryl group, a substituted aryl group, with the exception of R 1 and R 2 can not be simultaneously two methyl groups or form a cyclohexane when R is a 1,3-diisopropylphenyl group, and R 1 and R 2 can not be methyl and phenyl or form cyclohexane when R is tert-butyl.
  • the preferred iminium salts correspond to the formula (VIa) in which:
  • R represents a tert-butyl group; a phenyl group substituted with 3 methyl or ethyl groups in o, o 'and p positions; a phenyl group substituted with 2 isopropyl or tert-butyl groups in o and o 'position; a phenyl group substituted with 3 isopropyl or tert-butyl groups at o, o 'and p, R 1, R 2, which are identical or different, represent a methyl, ethyl, propyl, isopropyl, phenyl or substituted phenyl group;
  • R 1 and R 2 may be bonded together to form a spirocycle comprising from 3 to 10 atoms, R '3 represent a hydrogen atom, a methyl group,
  • R 4 , R ' 5 identical or different, represent a hydrogen atom, a methyl group.
  • the invention relates to the iminium salts corresponding to the formula (VIa) in which: R represents a phenyl group substituted with 2 isopropyl groups at the o and o 'position; a phenyl group substituted with 3 methyl or isopropyl groups at o, o 'and p,
  • R 1, R 2 identical or different, represent a methyl group, a phenyl group, a substituted phenyl group, or R 1 and R 2 may be bonded together to form a spirocycle comprising from 3 to 10 atoms,
  • R 4 , R ' 5 represent a hydrogen atom.
  • the preferred iminium salts which include two aryl groups, are schematized by the formula (Vlai).
  • the groups R s which are identical or different, represent a substituent chosen from alkyl or alkoxy groups having from 1 to 4 carbon atoms,
  • n is the number of substituents equal to 1, 2 or 3, preferably 2 or 3,
  • - R t represent one or more substituents having the meaning given above, - R 4 , R ' 5 , represent a hydrogen atom.
  • Z is preferably a chloride (in the form CI “ , HCI2 " or their mixture).
  • the yield given in the examples corresponds to the ratio between the number of moles of product formed and the number of moles of substrate involved.
  • an unsaturated reagent which is an allyl halide (1.3 equivalents) and an aldehyde ⁇ - disubstituted (1 equivalent) to which is added dropwise, a mixture of an aqueous solution containing 50% by weight of sodium hydroxide, an organic solvent and tetrabutylammonium bromide (4% molar) at 70-80 0 C (m.p. 'oil).
  • the organic solvent is toluene in all the examples with the exception of Examples 2 and 3 where it is 2-isopropylbenzene.
  • the mixture is stirred for 4.5 h at 70-80 0 C, cooled to room temperature and then extracted with distilled water.
  • the aqueous phase is extracted with the solvent used then the organic phase is dried over MgSO 4 and filtered on No. 4 sintered glass.
  • the solvent of the filtrate is evaporated under reduced pressure of approximately 50 mm of mercury (Rotavapor) and the filtrate is distilled under reduced pressure.
  • the toluene is then evaporated under reduced pressure of approximately 50 mm of mercury (Rotavapor), then the pellet is distilled under reduced pressure.
  • the medium is then filtered, the filtrate evaporated under reduced pressure of approximately 50 mm Hg (Rotavapor) and then distilled under reduced pressure.
  • the imine is dissolved in toluene (solvent) and the solution is cooled to 0 ° C. A bubbling of HCl gas is maintained in the solution at 0 ° C. for 5 hours.
  • reaction medium is heated at 80 ° C. for 12 hours: a white precipitate is observed (glass wool).
  • Sintered glass filtration No. 4 and washing with ether makes it possible to recover a fine white powder which corresponds to the cyclized product.
  • the yield obtained is 80%.
  • the imine is dissolved in toluene and the solution is cooled to 0 ° C.
  • a bubbling of HCl gas is maintained in the solution at 0 0 C for 5 hours.
  • the imine is dissolved in toluene and the solution is cooled to 0 ° C.
  • This white powder corresponds to the cyclized product.
  • the temperature is lowered to -78 ° C. and 25 ml of dry THF are added.
  • the THF is evaporated under a reduced pressure of 10 mm Hg.

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EP08736019A 2007-04-12 2008-04-09 Verfahren zur herstellung von carbenvorläufern des caac-typs und ihre verwendung zur herstellung besagter carbene Withdrawn EP2139853A1 (de)

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US8227371B2 (en) 2010-09-24 2012-07-24 Exxonmobil Chemical Patents Inc. Class of olefin metathesis catalysts, methods of preparation, and processes for the use thereof
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