EP1377376A1 - Catalyseurs pour substitution nucleophile, leur synthese, composition en contenant et leur utilisation - Google Patents

Catalyseurs pour substitution nucleophile, leur synthese, composition en contenant et leur utilisation

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Publication number
EP1377376A1
EP1377376A1 EP02732820A EP02732820A EP1377376A1 EP 1377376 A1 EP1377376 A1 EP 1377376A1 EP 02732820 A EP02732820 A EP 02732820A EP 02732820 A EP02732820 A EP 02732820A EP 1377376 A1 EP1377376 A1 EP 1377376A1
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EP
European Patent Office
Prior art keywords
advantageously
chosen
formula
nitrogen
use according
Prior art date
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Application number
EP02732820A
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German (de)
English (en)
French (fr)
Inventor
Vincent Schanen
Henri-Jean Cristau
Marc Taillefer
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Rhodia Chimie SAS
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Rhodia Chimie SAS
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Priority claimed from FR0105034A external-priority patent/FR2823451B1/fr
Priority claimed from FR0204522A external-priority patent/FR2838441B1/fr
Application filed by Rhodia Chimie SAS filed Critical Rhodia Chimie SAS
Publication of EP1377376A1 publication Critical patent/EP1377376A1/fr
Withdrawn legal-status Critical Current

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0239—Quaternary ammonium compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0255—Phosphorus containing compounds
    • B01J31/0267—Phosphines or phosphonium compounds, i.e. phosphorus bonded to at least one carbon atom, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, the other atoms bonded to phosphorus being either carbon or hydrogen
    • B01J31/0268—Phosphonium compounds, i.e. phosphine with an additional hydrogen or carbon atom bonded to phosphorous so as to result in a formal positive charge on phosphorous
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B39/00—Halogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
    • C07C17/20—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms
    • C07C17/202—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms two or more compounds being involved in the reaction
    • C07C17/208—Preparation of halogenated hydrocarbons by replacement by halogens of halogen atoms by other halogen atoms two or more compounds being involved in the reaction the other compound being MX
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/062—Organo-phosphoranes without P-C bonds
    • C07F9/065—Phosphoranes containing the structure P=N-
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/535—Organo-phosphoranes
    • C07F9/5355—Phosphoranes containing the structure P=N-
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions

Definitions

  • the present invention relates to a new method for producing nucleophilic substitutions, in particular of the SNA ⁇ type, and more particularly relates to new catalysts. Although the effect is less marked, it also relates to the use of these catalysts for SN 2 reactions.
  • the invention relates more particularly to aromatic nucleophilic substitution reactions involving the following reaction scheme:
  • R possible radical R possible radical n the number of GEA Electro-Attractor Group substituents
  • the leaving group can thus be a nitro group, advantageously a pseudohalogen, or preferably a halogen atom, especially with an atomic number greater than that of fluorine.
  • pseudohalogen is intended to denote a group whose departure leads to an oxygenated anion, the anionic charge being carried by the chalcogen atom and whose acidity is at least equal to that of acetic acid, advantageously at the second acidity of sulfuric acid and, preferably, that of trifluoroacetic acid.
  • pKa for medium to high acidities from carboxylic acids to acetic acid and place on the Hammett constants scale (see Figure 1 ) from trifluoroacetic acid.
  • the leaving group is a nitro group
  • the latter is generally replaced by a chlorine or fluorine atom.
  • most of these reagents require operating at very high temperatures and the mechanism does not always turn out to be a nucleophilic substitution.
  • the departure from the nitro group leads to the formation of oxygenated and halogenated nitrogen derivatives which are particularly aggressive with respect to the substrate, or even explosive.
  • the aryl radical to be transformed is preferably depleted in electrons and has an electronic density at most equal to that of benzene, at most close to that of a chlorobenzene, preferably a dichlorobenzene.
  • This depletion may be due to the presence in the aromatic (six-membered) cycle of a heteroatom such as, for example, in pyridine, quinoline (depletion in this case involves a six-membered ring).
  • the depletion is significant enough for the substitution reaction to be very easy and does not require any specific additional activation.
  • Depletion of electrons can also be induced by electron-withdrawing substituents present on this aromatic cycle. These substituents are preferably selected from withdrawing by an inductive effect or effect mesomeric groups as defined in the reference book in Organic Chemistry "Advanced Organic Chemistry” by J. MARCH, 3rd edition, Wiley publisher, 1985 (see in particular pages 17 and 238).
  • one of the techniques most used to manufacture a fluorinated derivative consists in reacting a halogenated aromatic derivative, generally chlorinated, to exchange the halogen (s) with one or more fluorine (s). ) of mineral origin.
  • a halogenated aromatic derivative generally chlorinated
  • fluorine (s). ) of mineral origin e.g., sodium fluorides and especially potassium, cesium and / or rubidium.
  • an alkali metal fluoride is used, most often of a high atomic weight such as for example sodium fluorides and especially potassium, cesium and / or rubidium.
  • the fluoride used is potassium fluoride which constitutes a satisfactory economic compromise.
  • reaction is slow and, due to a long residence time, requires significant investment.
  • This technique is generally used at high temperatures which can reach around 250 ° C., or even 300 ° C. in the case of nuclei with little depletion of electrons, that is to say say in the area where the most stable organic solvents begin to decompose.
  • one of the aims of the present invention is to provide nucleophilic substitution catalysts which allow in particular a catalysis of the SN 2 and especially SNA ⁇ reactions.
  • Another object of the present invention is to provide nucleophilic substitution catalysts which allow in particular a catalysis of SNA initiativess reactions, even when the nucleus seat of said SNA ⁇ is only slightly depleted in electrons.
  • Another object of the present invention is to provide nucleophilic substitution catalysts which are also phase transfer agents. Another object of the present invention is to provide nucleophilic substitution catalysts which have a fairly high decomposition temperature, for example at least 200 ° C, advantageously 250 ° C, and even 300 ° C.
  • the Pn are chosen from the metalloid elements of column V with a period greater than that of nitrogen;
  • - Z is a metalloid element of column V, advantageously distinct from Pn; preferably a nitrogen (N, P, As, Sb).
  • the fact that one of Ri to R 6 is hydrogen is not preferred.
  • the compounds of formula (I) can be neutral and in this case are amphoteric, in other words carriers in the same molecule of the cationic function exposed in formula (I) and of the anionic function ensuring electrical neutrality; but the easiest compounds of formula (I) are cationic compounds and are advantageously introduced in the form of a salt of formula (II):
  • - X " is a counterion chosen from anions and mixtures of anions, which anions and mixtures of anions are advantageously chosen from monovalent anions;
  • said hydrocarbon radicals Ri, R 2 , R 3 , Rt, R5, and R 6 are generally chosen from:
  • phosphino groups such as dialkoylphosphino alkyloylphosphino and especially diarylphosphino; but, especially when Pn is phosphorus, it is preferable that there are at most two, advantageously, at most one such group per atom of Pn;
  • the compounds where the R 4 , R 5 , or even R 6 are phosphinimino are easy to synthesize.
  • these phosphinimino mention may be made of those in which the phosphorus carries aryls, alkyls or dialkoylamino.
  • the aryls entering into the above compound are advantageously homocyclic taken in the sense of anonymous to heterocyclic.
  • alkyl is taken in its etymological sense from the rest of an alcohol from which the OH function has been removed. Thus it essentially comprises the radicals, the free bond of which is carried by a carbon atom of hybridization sp 3 , which carbon atom is linked only to carbons or to hydrogens.
  • the alkyls which are substituted by atoms and / or functions (according to the applications it is preferable to avoid the parasitic reactions of choosing functions which are inert under the conditions for implementing the invention) and in particular those which carry ether function (s) and in particular the mono-oligo- or poly-ethoxylated sequences obtained epoxides in particular of ethylene and / or of peralkylated amine function, those which are substituted by halogens, those which carry aromatic nucleus (s).
  • Said alkyls can also carry phosphonium or quaternary ammonium functions
  • the Ri, R 2 , R3, 4 , R5, and Re advantageously have at most 20 carbon atoms and, unless it is linked to a polymer, the molecule has a total of at most 100 atoms carbon, preferably at most 60 carbon atoms.
  • Ri, R 2 , R 3 Ri, R5, and R 6 represent a polymer arm; this arm is linked to the corresponding Pn atom via a link with a carbon atom of aliphatic or aromatic nature or via a link with an imino or amino group.
  • Ri, R 2 , R 3 are identical. The same goes for R, R 5 , and RQ. Ri, R 2 , R 3 , R 4 , R5, and R ⁇ can be linked together and form cycles.
  • R 3 , R4, R 5 , and R 6 are the same, is easier and therefore less expensive. To this extent, they are therefore preferred. However, the activity of compounds not having this symmetry around Z is very often excellent.
  • this carbon atom can be of sp 3 hybridization aliphatic, or sp 2 hybridization, that is to say mainly of aromatic nature due to the instability of the vinyl groups. Links with atoms of an aromatic nature are preferred. Another kind of link is preferred, it is the link through the nitrogen atom of an amino function or an imine function.
  • At least 3, advantageously at least 4, preferably at least 5, more preferably all of the R 1 t R 2 , R3, R4, R5, and Re are linked to the Pn through atom of aromatic carbon and / or nitrogen atom of amino function or peralkylated imine.
  • the peralkylated imines are phosphonimines
  • the counterions are advantageously chosen from anions and mixtures of anions X "which are not very nucleophilic, that is to say when they are unique, are such that XH has a pKa at most equal to 3, advantageously at 2, preferably 1, more preferably zero and when they consist of a mixture of anions at least one of the anions is not very nucleophilic.
  • Ar- ( ⁇ ) - where Ar is an aromatic radical in which the nucleus carrying ⁇ is depleted in electrons either because it contains at least one heteroatom in its cycle, or because the sum of the ⁇ p of its substituents, except the ⁇ , is at least equal to 0.2, advantageously to 0.4, preferably to 0.5; the substituents can be leaving groups likely to give rise to a new substitution and thus to be noted ⁇ , in an SNA ⁇ later; - where ⁇ is a leaving group, advantageously in the form of an anion ⁇ " ; to the action of a nucleophilic agent capable of exchanging with the or at least one of the substituents ⁇ in the presence of a catalyst of formula (I).
  • the molar ratio between the catalyst and the nucleophilic agent used in the reaction is at least equal to 0.1% o, advantageously 0.5% o, preferably 1% o, more preferably 0.5 %.
  • the molar ratio between the catalyst and the substrate used in the reaction is at least equal to 0.1% o, advantageously 0.5% o, preferably 1% o, more preferably 0.5% .
  • ⁇ " is less nucleophilic than the nucleophilic agent with which it is going to be exchanged; as the nucleophilia scales are difficult to use, the person skilled in the art can use the empirical rule that ⁇ H is advantageously more acid than the nucleophile in the form on Avenue may be a nitro or quaternary ammonium group, but it is preferable that it is a pseudohalogen group or preferably a halogen atom chosen from chlorine, bromine and iodine.
  • pseudohalogen is intended to denote a group the departure of which leads to an oxygenated anion, the anionic charge being carried by the chalcogen atom and the acidity of which, expressed by the Hammett constant, is at least equal to that of the acetic acid, advantageously at the second acidity of sulfuric acid and preferably that of trifluoroacetic acid.
  • the nucleophilic substitution reaction being relatively facilitated when ⁇ represents an iodine atom, the claimed process is more particularly interesting when ⁇ symbolizes a chlorine, bromine or pseudohalogen atom.
  • the aromatic substrate thus substituted has an electronic density at most equal to that of phenyl, advantageously at most close to that of a chlorophenyl and preferably a difluorophenyl.
  • This depletion may also be due to the presence in the aromatic cycle of a heteroatom such as, for example, in pyridine, quinoline. It is important to emphasize that this type of depletion is only observed when Ar symbolizes a compound having a 6-membered ring and the heteroatom belongs to column V (essentially nitrogen or phosphorus) as defined in the table in the periodic classification of the elements published in the supplement to the Bulletin of the Chemical Society of France in January 1966.
  • the or at least one of the groups R is an electron-withdrawing substituent and not leaving and more preferentially is different from a carbon substituent.
  • the substituent (s) R when they are attractors can be chosen from halogen atoms and the following groups: - NO 2
  • Alk representing a hydrogen, advantageously an alkyl group, linear or branched, preferably from Ci to C 4 .
  • R groups As examples of preferred R groups, mention may more particularly be made of halogen atoms and the nitro group.
  • the electron-withdrawing substituent (s) R are more preferably located in the ortho and / or para position with respect to the leaving group (s) ⁇ .
  • nucleophilic agent intended to replace the leaving group (s) X at the level of the aromatic substrate, it can be generated in situ during the irradiation reaction.
  • nucleophilic agent capable of being used according to the invention there may be mentioned in particular:
  • Nitrogen nucleophilic derivatives are of particular interest in the context of the claimed process.
  • Another object of the present invention is to provide a process which is particularly useful for carrying out exchange reactions between fluorine and the halogens of the higher atomic number present on the aromatic substrate, and in particular the exchange reactions between fluorine and chlorine.
  • Reverse exchange reactions that is to say the replacement of a halogen by a halogen of higher rank, are also possible.
  • this type of reaction is of less interest and is moreover more difficult to carry out. Nevertheless, it is within the reach of those skilled in the art to take advantage of the teaching of the present process to carry out other exchange reactions, and in particular these reverse exchange reactions.
  • the fluoride is a fluoride of an alkali metal of atomic number at least equal to that of sodium and preferably is a potassium fluoride.
  • the fluoride, alkaline or alkaline earth is at least partially present in the form of a solid phase.
  • reaction is carried out at a temperature lower than that retained for a reaction carried out with a usual catalyst (whose paradigm is tetramethylammonium).
  • the reaction is generally carried out in a solvent and, in this case, it is preferable to carry out the reaction at a temperature of at least 10 ° C., advantageously 20 ° C, preferably 40 ° C lower than that of the temperature limit usually accepted for said solvent used.
  • the heating is carried out partially or completely by microwave of the present invention; in this case it is preferable that the microwaves are emitted in short periods (from 10 seconds to 15 minutes) alternating with cooling phases.
  • the respective durations of the microwave emission periods and the cooling periods are chosen so that the temperature at the end of each microwave emission period remains below a fixed initial temperature which is generally lower than the strength of the ingredients in the reaction mixture.
  • the power released by the microwaves is then chosen so that, for a fixed initial temperature, generally that of operation, it is equivalent to the energy evacuated by the cooling system and this to heat released or absorbed by the reaction.
  • Such an actinic heating method also has the advantage of being compatible with a continuous operating mode.
  • This mode of use advantageously makes it possible to overcome the problems of heat exchange which may be generated during the opening and closing operations of the reactor where the microwaves are emitted.
  • the materials to be activated are introduced continuously via an inlet orifice within the reactor where they undergo activation by microwave and the products are continuously removed from said reactor via an outlet orifice.
  • actinic heating by microwaves it is recommended to use a power released by microwaves of between 1 and 50 watts per milliequivalent of aromatic substrate. It is also desirable to comply with the constraint that the power released by the microwaves is between 2 and 100 watts per gram of reaction mixture.
  • the catalyst according to the invention can be used concomitantly with a catalyst deemed to be a phase transfer catalyst, especially when this catalyst is a catalyst of cationic nature. Such concomitant use is all the more judicious since the mechanism of action seems different.
  • phase transfer catalysts that can be used are generally oniums, that is to say they are organic cations whose charge is supported by a metalloid.
  • oniums mention should be made of ammoniums, phosphoniums and sulfoniums.
  • other phase transfer catalysts can also be used as soon as these phase transfer catalysts are positively charged.
  • It may also be encrypted cations, for example crown ethers encrypting alkalis.
  • phase transfer catalysts can be used in the presence or in the absence, preferably in the presence of a particularly heavy alkaline cation and therefore of high atomic rank such as cesium and rubidium.
  • a dipolar aprotic solvent is generally used, a solid phase consisting at least partially of alkaline fluorides and a cation which promotes the reaction, said cation being a heavy alkali or an organic phase transfer agent, an agent of cationic nature.
  • the content of alkaline cation when used as promoter is advantageously between 1 and 5%, preferably between 2 and 3 mol% of the nucleophilic agent used.
  • These domains are closed domains, that is to say that they have their limits.
  • the reagent can include, as promoter, phase transfer agents which are oniums (organic cations whose name ends with onium).
  • Oniums generally represent 1 to 10%, preferably 2 to 5 mol% of the aromatic substrate, the counter ion is indifferent but most often halogen.
  • the preferred reagents are tetraalkylammoniums of 4 to 28 carbon atoms, preferably of 4 to 16 carbon atoms. Tetraalkylammonium is generally tetramethylammonium. Mention should also be made of phosphoniums and in particular phenylphosphoniums which have the advantage of being stable and relatively unhygroscopic, however the latter are relatively expensive.
  • the halex-type aprotic solvent advantageously has a significant dipole moment.
  • its relative dielectric constant epsilon is advantageously at least equal to around 10, preferably the epsilon is less than or equal to 100 and greater than or equal to 25.
  • the oniums are chosen from the group of cations formed by the columns VB and VIB as defined in the table of the periodic classification of the elements published in the supplement to the Bulletin of the departments Chimique de France in January 1966, with respectively four or three hydrocarbon chains .
  • said suspended solid In general, it is known that a fine particle size has an influence on the kinetics.
  • said suspended solid it is desirable for said suspended solid to have a particle size such that its dgo (defined as the mesh allowing 90% by mass of the solid to pass) is at most equal to 100 ⁇ m, advantageously at most equal to 50 ⁇ m, of preferably at most equal to 200 ⁇ m.
  • the lower limit is advantageously characterized by the fact that the d-io of said suspended solid is at least equal to 0.1 ⁇ m, preferably at least equal to 1 ⁇ m.
  • the ratio between said nucleophilic agent, preferably alkaline fluoride and said substrate is between 1 and 1.5, preferably around 5/4 relative to the stoichiometry of the exchange.
  • the mass content of solids present in the reaction medium is advantageously at least equal to 1/5, advantageously 1/4, preferably 1/3.
  • the agitation is advantageously carried out so that at least 80%, preferably at least 90% of the solids, is kept in suspension by the agitation.
  • the reaction is advantageously carried out at a temperature ranging from approximately 150 to approximately 250 ° C.
  • a temperature ranging from approximately 150 to approximately 250 ° C.
  • approximately is used to highlight the fact that the values which follow it correspond to mathematical roundings and in particular that, in the absence of comma, when the digit (s) furthest to the right of a number are zeros, these zeros are position zeros and not significant figures, except of course if specified otherwise. It should however be emphasized that when the temperature increases, the kinetics increase but that the selectivity decreases.
  • Another object of the present invention is to provide a composition capable of serving as a nucleophilic substitution reagent, in particular an aromatic.
  • composition comprising: • a polar aprotic solvent;
  • Another object of the invention is to provide, in addition to that of having supplied a new family of new compounds useful as nucleophilic substitution catalysts and having a marked catalytic character.
  • Another object of the present invention is to provide a process for the synthesis of the compounds used or usable as a nucleophilic substitution catalyst of order 2 and in particular of nucleophilic substitution called SN ar .
  • R3. 4, 5 and R 6 is greater than 12, preferably at least equal to 14, advantageously at least equal to 16.
  • the limitation on the number of alkyl derivatives is linked to the fact that, according to the present invention, it has been shown that it is desirable for the substituents R 1 to R 6 to exhibit above all a donor character by mesomeric effect in order to better delocalize the positive charge.
  • the alkyl chains with a carbon number greater than 5 may be of interest for the compatibility of the catalyst with solvents of low polar character, that is to say the solvents which are not miscible in all proportions with water.
  • the final product can be obtained by quaternization of the Pn which remains trivalent using a compound chosen from R 4 -X ', R 5 -X' or R 6 -X '. or X ′ is an advantageously halogen leaving group preferably of rank at least equal to that of chlorine; including Brome and iodine.
  • the reaction can be written as follows:
  • the iminoid is condensed with a phosphine already carrying two of the final substituents, here R 4 and R 5 .
  • one of the Pn is advantageously P.
  • Z is advantageously nitrogen.
  • the anion of the iminoid is transformed into cation by oxidation, advantageously by means of a positive halogen (commonly noted in the case of bromine by Br + ) or molecular, most often bromine and is brought into contact with a trisubstituted Pn (R4) (Rs) (Re) Pn; giving thus directly a compound according to the present invention.
  • a positive halogen commonly noted in the case of bromine by Br +
  • Rs trisubstituted Pn (R4) (Rs) (Re) Pn
  • one of the Pn is advantageously P, preferably both.
  • Z is advantageously nitrogen.
  • the synthesis can be carried out by reacting a trisubstituted phosphinimine compound with a halophosphonium halide, which phosphonium carries three hydrocarbon substituents.
  • a halophosphonium halide which phosphonium carries three hydrocarbon substituents.
  • phosphiniminophosphonium bromide can be carried out by reacting phosphinimines with the dibromophosphoranes corresponding to the desired salt.
  • the phosphinimines are obtained by deprotonation of the corresponding aminophosphonium salt in the presence of a strong base such as sodium amide.
  • the reaction can be written as below: PhsPBrc
  • the R 'can for example correspond to Ri, R 2 and R 3 and the R can correspond to R 4 , R 5 and R ⁇ or vice versa.
  • the starting phosphonimines are generally obtained by the action of an equivalent of n-butyllithium as a base on an aminophosphonium halide in general of bromide.
  • Some phosphinimines are commercial.
  • Dibromophosphorane is prepared beforehand by simple addition of a stoichiometric amount of dibroma to the appropriate phosphine. As indicated in the paradigmatic equation below:
  • the R 'can for example correspond to Ri, R 2 and R 3 and the R can correspond to R, R 5 and R & or vice versa.
  • the synthesis of these symmetrical or asymmetrical compounds is carried out by means of an intermediate called the phosphonium azayldiide.
  • This reaction can be schematized as below, it being understood that in this example, the phenyls can be replaced by Ri, R 2 , R 3 and Ar 3 can be replaced by R 4 , R 5 and R 6 . Equation # 3
  • the R 'can for example correspond to R-i, R2 and
  • R 3 and R can correspond to R 4 , R 5 and R ⁇ or vice versa.
  • the tubes are closed with a septum and a screw cap, then heated with stirring for 4 h at 150 ° C. After returning to ambient temperature, approximately 10 g of water are added, then 5 g of dichloromethane, after decantation and separation of the organic and aqueous phases, the aqueous phase is back-extracted twice with 5 g of dichloromethane. The different organic phases are collected and analyzed by CPG. Loading table
  • TMAC tetra-methyl-ammonium chloride
  • Tetrakis tetrakis- (diethylamino) -phosphonium bromide
  • Ph 4 PBr tetra-phenyl-phosphonium bromide
  • PPNCI bis (triphenylphosphoranylidene) -ammonium chloride of formula
  • the tubes are closed with a septum and a screw cap, then heated with stirring for 4 h at 170 ° C. After returning to ambient temperature, approximately 10 g of water are added, then 5 g of dichloromethane, after decantation and separation of the organic and aqueous phases, the aqueous phase is back-extracted twice with 5 g of dichloromethane. The different organic phases are collected and analyzed by CPG.
  • TMAC tetra-methylammonium chloride
  • Tetrakis terakis- (diethylamino) -phosphonium bromide
  • Ph4PBr tetra-phenyl-phosphonium bromide
  • PPNCI Bis (triphenylphosphoranylidene) -ammonium chloride.
  • the catalyst according to the invention which gives both the best conversion rate but also the one which gives the best yield of difluorinated product.
  • the tubes are closed with a septum and a screw cap, then heated with stirring to 210 ° C. for the time indicated in the table. After returning to ambient temperature, approximately 10 g of water are added, then 5 g of dichloromethane, after decantation and separation of the organic and aqueous phases, the aqueous phase is back-extracted twice with 5 g of dichloromethane. The different organic phases are collected and analyzed by CPG.
  • the catalyst according to the invention is on the one hand that which gave the highest conversion rate but on the other hand the only one which gave a little difluorination.
  • the tubes are closed by a septum and a screw cap, then heated with stirring for 3 h at 150 ° C. After returning to ambient temperature, approximately 10 g of water and 5 g of dichloromethane are added, then again 5 g of dichloromethane. After decantation and separation of the organic and aqueous phases, the aqueous phase is back-extracted twice with 5 g of dichloromethane. The different organic phases are collected and analyzed by HPLC. Chartaement table
  • the tubes are closed with a septum and a screw cap, then heated with stirring for 3 h at 210 ° C. After returning to ambient temperature, approximately 10 g of water and 5 g of dichloromethane are added, then again 5 g of dichloromethane. After decantation and separation of the organic and aqueous phases, the aqueous phase is back-extracted twice with 5 g of dichloromethane. The different organic phases are collected and analyzed by CPG.
  • the organic phase is then dried over MgSO 4 and concentrated to dryness for the various treatments.
  • b) General procedure for passing from I to Br The pure iodide obtained is redissolved in dichloromethane and washed with an aqueous solution of silver nitrate (2 eq). The organic phase is then washed with a solution of distilled water in order to remove the remains of suspended silver iodide. The organic phase will then undergo 3 washes with an aqueous NaBr solution (2.5 eq; 1.5 eq; 0.5 eq). The organic solution is finally dried over MgSO then concentrated to dryness under reduced pressure, thus making it possible to isolate the pure bromine compound.
  • the solution obtained is filtered and the precipitate purified by simple washing, first with a solution of 30 ml of ethanol and then with a solution of 50 ml of ether. We obtained the tribrominated salt of the expected product.
  • the tribrominated salts obtained are taken up in a solution of dichloromethane and washed with an aqueous solution of sodium sulfite (2 eq). Discoloration of the organic phase is then rapidly observed, a characteristic sign of the reduction of the trihalides. The organic phase is dried over
  • reaction mixture is filtered and the precipitate containing the expected product recovered. This is taken up in a minimum of dichloromethane to which a few drops of ethanol will be added until the slight haze disappears completely. Adding a large volume of ether will remove much of the impurities.
  • the ethereal phase is then concentrated to dryness, taken up in ether and left at low temperature overnight.
  • the product in monobrominated form is recovered pure by simple filtration and the solid dried over P2O5 overnight at
  • the solution obtained is evaporated to dryness under reduced pressure.
  • the residue recovered is taken up in ether, then filtered.
  • the pasty, semi-solid product is taken up in dichloromethane and washed with a solution of distilled water.
  • the organic phase is dried over MgSO 4 , filtered and then concentrated to dryness.
  • the product is then suspended in ether and left overnight at low temperature.
  • the pasty solid contained in the ethereal phase is triturated in a cold alcohol bath at -70 ° C and the solution is filtered.
  • the pure product is finally dried in a desiccator on

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EP02732820A 2001-04-12 2002-04-12 Catalyseurs pour substitution nucleophile, leur synthese, composition en contenant et leur utilisation Withdrawn EP1377376A1 (fr)

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Application Number Priority Date Filing Date Title
FR0105034 2001-04-12
FR0105034A FR2823451B1 (fr) 2001-04-12 2001-04-12 Catalyseurs de substitution aromatique nucleophile, composition en contenant et utilisation pour une substitution sn ar
FR0204522A FR2838441B1 (fr) 2002-04-11 2002-04-11 Composes presentant un role catalytique dans les echanges de substitutions nucleophiles et procede de synthese de ces composes
FR0204522 2002-04-11
PCT/FR2002/001286 WO2002092226A1 (fr) 2001-04-12 2002-04-12 Catalyseurs pour substitution nucleophile, leur synthese, composition en contenant et leur utilisation

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DE102004033525A1 (de) * 2004-07-08 2006-02-02 Lanxess Deutschland Gmbh Verbessertes Verfahren zur Herstellung kernfluorierter Aromaten
US7304172B2 (en) * 2004-10-08 2007-12-04 Cornell Research Foundation, Inc. Polycarbonates made using highly selective catalysts
US9162953B2 (en) * 2006-07-05 2015-10-20 Centre Nationale De Recherche Scientifique Iron-copper co-catalyzed process for carbon-carbon or carbon-heteroatom bonding
JP5421118B2 (ja) * 2006-12-22 2014-02-19 シエル・インターナシヨネイル・リサーチ・マーチヤツピイ・ベー・ウイ オレフィンモノマーのオリゴマー化用配位子及び触媒
FR2915200B1 (fr) * 2007-04-20 2009-07-03 Centre Nat Rech Scient Procede de preparation de ligands de type phosphines butadieniques,leurs complexes avec le cuivre,et leurs applications en catalyse
US9272274B2 (en) 2007-12-06 2016-03-01 Centre National De La Recherche Scientifique (C.N.R.S.) Catalytic system for cross-coupling reactions
FR2928925B1 (fr) 2008-03-19 2011-01-07 Centre Nat Rech Scient Complexes de bore ou d'aluminium, et leurs utilisations.
JP5300123B2 (ja) * 2008-03-24 2013-09-25 広栄化学工業株式会社 アンモニウム塩及びそれを用いた帯電防止剤
JP5481628B2 (ja) * 2008-07-28 2014-04-23 国立大学法人東北大学 高熱安定性を有する機能性フォスファジド
WO2011008725A2 (en) * 2009-07-13 2011-01-20 Massachusetts Institute Of Technology Metal-catalyzed carbon-fluorine bond formation
CN103553974A (zh) * 2013-10-31 2014-02-05 上海华谊（集团）公司 一种n-烷基共轭离子型季铵盐的制备方法
CN108586257B (zh) * 2018-05-03 2020-12-22 浙江解氏新材料股份有限公司 一种对氟硝基苯的制备方法

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US4069262A (en) * 1977-03-07 1978-01-17 E. I. Du Pont De Nemours And Company Preparation of 2-fluoronitrobenzene
US4140719A (en) * 1977-10-31 1979-02-20 Merck & Co., Inc. Solid-liquid phase transfer catalysis improved method of preparing 2,4-difluoroaniline
US5045632A (en) 1989-05-25 1991-09-03 The Dow Chemical Company Novel bis(phosphoranylidene) ammonium salts
DE59205077D1 (de) * 1991-07-17 1996-02-29 Hoechst Ag Verfahren zur Herstellung von Chlorfluornitrobenzolen
US5401814A (en) * 1993-10-13 1995-03-28 The Dow Chemical Company Process for the preparation of thermoplastic poly(hydroxy ethers)
DE19702282C2 (de) 1997-01-23 1998-11-19 Hoechst Ag Katalysator für Halex-Reaktionen

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CN1505547A (zh) 2004-06-16
CN100482344C (zh) 2009-04-29
CA2442782A1 (fr) 2002-11-21
HUP0303945A2 (hu) 2004-03-29
US20040147390A1 (en) 2004-07-29
MXPA03009212A (es) 2004-01-29
US7217842B2 (en) 2007-05-15
JP2004524969A (ja) 2004-08-19
US20070225524A1 (en) 2007-09-27
WO2002092226A1 (fr) 2002-11-21

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