Classifications

• • 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
• • 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

Definitions

• the present invention relates to a process for fluorodenitrogenation; it relates more particularly to a process allowing the elimination of a nitrogen bound to a carbon by a multiple bond to give a corresponding fluorinated derivative.
• the invention relates to the transformation of a nitrile function with a trifluoromethyl group or of an imine with a difluoromethylene group.
• Fluoroalkylated derivatives are increasingly used in pharmacy and agrochemistry. However, their synthesis is difficult or uses expensive reagents such as Ruppert's reagent or requires very harsh operating conditions which are not suitable for all substrates.
• one of the aims of the present invention is to provide a process which completes the range of access routes to polyfluorinated derivatives on the same carbon. Furthermore, the synthesis of functions having a multiple carbon-nitrogen bond is fairly easy, whether it be the imination reactions or the reactions forming nitrile functions, either by grafting a cyanide anion, or, for example, by dehydration an amide function. This is why one of the aims of the present invention is to provide a method which makes it possible to transform a function having a multiple carbon-nitrogen bond to give a function carrying fluorines on carbon, preferably in a number equal to the multiplicity of the link.
• Another object of the present invention is to provide a process which makes it possible to transform the triple carbon-nitrogen bond of the nitrile function into a carbon tripling carrying a fluorine atom, namely the trifluoromethyl radical.
• hydrofluoric acid complexes targeted are those which consist or comprise at least one defined compound chosen from those consisting of the association of a Bronstedt base with a defined number n of hydrofluoric acid, n being equal to less than 2, advantageously at and at most at 20, advantageously 15, preferably 10.
• bases can be said under the formula: B (HF) n
• the primary, secondary and preferably tertiary amines lead to reagents comprising few HF groups (at most 5, generally less) and less suitable for the reaction targeted by the present invention than bases of aromatic heterocyclic type, the, or at least one, of the heteroatoms is chosen from column V of the periodic table (nitrogen column).
• HF bases complexes
• HF bases complexes
• the complexes between metallic fluorides (in particular alkaline such as KF, CsF, ...) complexed with HF do not constitute a preferred mode:
• this concept does not include the complexes between metallic fluorides ( in particular alkalis such as KF, CsF, etc.) complexed with HF.
• the quantity [expressed in equivalents of alkali metal and ammonium cations] is at least equal to 1 time, advantageously at least 2 times, that of hydrogen in the form of free protons or as HF base complexes, including F-HF.
• the preferred hydrofluoric acid complexes are those which involve a pyridine ring.
• the compounds capable of constituting a nitrosonium precursor (NO + ) under the operating conditions are advantageously chosen from the salts and esters of nitrous acid and the nitrosonium halides.
• the nitrosonium halides can be used in the presence of Lewis acids. Lewis acid can be introduced simultaneously into the reaction mixture in the form of a complex of said nitrosonium halide with a Lewis acid.
• nitrosonium halides it is preferable to use halides which, once released, are unlikely to interfere with the reaction.
• nitrosonium fluoride as the halide, or even nitrosonium chloride insofar as it is possible to drive off any hydrochloric acid thus formed from the reaction medium.
• the Lewis acids used to potentiate the precursors of nitrosonium are advantageously chosen from fluorinated derivatives. Among these fluorinated derivatives, mention may be made of BF 3 , SbF 3 and SbF 5. The preferred is BF 3 .
• the precursor element, or source, of nitrosonium can advantageously be nitrosonium fluoroborate. It should be mentioned that it is preferable that the amount of Lewis acid, especially if it is strong, is not significantly greater than the stoichiometric amount relative to the substrate carrying said multiple carbon-nitrogen bond.
• the Lewis acid can be in a sub-stoichiometric amount relative to said substrate and, in particular, in a catalytic amount.
• the compound capable of constituting a nitrosonium precursor is not in an excessively clearly over-stoichiometric amount, in particular it is preferable that the amount of said precursor is at most equal to 2 times the stoichiometric amount.
• the best reaction medium consists of an acid base complex, that is to say a complex between a Bronstedt base and hydrofluoric acid molecules, with possibly an excess of hydrofluoric acid so that the ratio between the basic functions capable of giving the acid base complexes and the total amount of HF compounds in the medium, including the molecules involved in the complex, is at least 5, advantageously 7, it is a molar ratio, this ratio can be assimilated to n but, in this case, it can be fractional.
• the quantity of hydrofluoric acid, free and in the form of acid base complex must be very much greater than the stoichiometric quantity necessary for the replacement of the CN bonds by CF bonds. A ratio greater than 2 times the stoichiometry and even greater than 3 times the stoichiometry allows acceptable results to be obtained.
• the acid base complex is advantageously a complex between a nitrogen base and hydrofluoric acid.
• This nitrogenous base is advantageously a soft base, such as an aniline depleted in electrons or more preferably a pyridine nucleus.
• Olah's reagent has been shown to be one of the most successful.
• said multiple carbon-nitrogen bond is a nitrile bond, or nitrile function.
• the functions corresponding to multiple carbon-nitrogen bonds can - be aromatic or aliphatic
• the functions corresponding to multiple carbon-nitrogen bonds are advantageously conjugated with other unsaturations, in particular said multiple carbon-nitrogen function is advantageously conjugated with an aromatic nucleus.
• This aromatic nucleus can be of any type but it gives particularly satisfactory results when this nucleus is of the phenyl type as in benzonitrile.
• the depletion of the aromatic nucleus advantageously six-membered, seems to favor the reaction.
• This depletion may be either due to the presence of electron-attracting groups in the medium, or to the presence of a heteroatom in a six-membered aromatic heterocycle as in pyridine.
• the reaction can be carried out at various temperatures but it is preferable that the temperature is between ambient and 150 ° C, preferably between 40 ° C and 100 ° C.
• the pressure is ambient or higher than ambient.
• the reaction can be carried out under HF pressure or under autogenous pressure obtained by simple heating of the reaction medium.
• a very acidic medium that is to say containing only hydrofluoric acid and possibly a strong Lewis acid such as BF
• a duplication compound corresponding to the creation of a carbon-carbon bond between two carbons originating from the nitrile function, thus giving a tetrafluorinated duplicate product on the two carbons initially carrying multiple carbon-nitrogen functions.
• Example 1 Formation of trifluoromethylbenzene from benzonitrile 1.03 g (0.01 mol) of benzonitrile are added to 14.3 g of HF-pyridine (70/30 w / w or about 10 HF for a pyridine; that corresponds to 50 molar equivalents of HF for 1 benzonitrile) in a polypropylene Erlenmeyer flask. 1.17 g of NOBF 4 (0.01 mol) or 0.69 g of NaNO 2 (0.01 mol) are then added in portions. The medium is then heated at 55 ° C for 48 h (in the case of NOBF 4 ) or 35 h in the case of NaNO 2 .
• reaction medium After cooling to 0 ° C, the reaction medium is hydrolyzed with ice, then extracted with dichloromethane. After elimination of the dichloromethane by distillation, the reaction crude is analyzed by GC (internal standard). The performance of the reactions is indicated in the table below. Recall that the transformation rate corresponds to the percentage of substrate transformed during the reaction.
• the reaction yield, or RR corresponds to the yield in the desired product, here trifluoromethylbenzene, relative to the initial substrate introduced.
• Example 2 Formation of trifluoromethylparanitrobenzene from paranitrobenzonitrile The procedure is taken from the previous example. The results are shown in the following table. These results were measured by vapor phase chromatography.
• Trifluorination of p-nitrobenzonitrile The percentages are calculated by CPV.

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• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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• 2003
  • 2003-12-18 FR FR0314881A patent/FR2864076B1/fr not_active Expired - Fee Related
• 2004
  • 2004-12-15 EP EP04805714A patent/EP1694616A2/fr not_active Withdrawn
  • 2004-12-15 WO PCT/FR2004/003241 patent/WO2005061417A2/fr not_active Application Discontinuation
  • 2004-12-15 CN CNA200480041161XA patent/CN1910123A/zh active Pending

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