Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C263/00—Preparation of derivatives of isocyanic acid
  • C07C263/16—Preparation of derivatives of isocyanic acid by reactions not involving the formation of isocyanate groups
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
  • C07B39/00—Halogenation

Definitions

• the subject of the present invention is a process for the synthesis of fluorinated compounds using carbamoyl fluoride as the fluorine source, which is in equilibrium with isocyanate and hydrofluoric acid.
• the present invention relates more particularly to the synthesis of compounds having both a perfluorinated carbon, or in any case perhalogenated carbon, and an isocyanate function, in particular an isocyanate function deriving from an aniline function.
• Perhalogenated carbon is a carbon of an aliphatic nature, that is to say that it is of sp 3 hybridization.
• perhalogenated carbon is meant a carbon of nature sp 3 , not carrying hydrogen and comprising, in addition to its link with the part of the molecule carrying the isocyanate function, at most 2, advantageously at most 1, radicals, all the other atoms being halogens; said radicals are advantageously chosen from the electron-withdrawing groups and this, especially when there are 2.
• the carbons carrying two halogens and one hydrogen are capable of being treated like the perhalogenes In the strict sense. They are, however, more lazy.
• the carbons carrying the exchangeable or exchanged halogens are also designated by the term of halophore (s).
• halophore s
• compounds comprising a perhalogenated and especially perfluorinated aliphatic atom have become increasingly important in the field of agrochemistry and pharmacy.
• These perfluorinated products most often comprising a perfluoromethyl or perfluoroethyl radical have physiological properties which make the molecules which compose them particularly active.
• the fluorinating agent is liquid hydrofluoric acid
• the intermediate substrate or the starting substrate are isocyanates.
• anilines carrying trifluoromethyl groups mention may therefore be made of the Western Chemical Corporation patent No. EP-A-129214 and the patent of the applicant's predecessor in law, namely the European patent registered in the name of Rhône-Poulenc Spéciality Chimiques and issued under the number EP-B-152 310.
• one of the aims of the present invention is to provide a fluorination process which does not require a large excess of hydrofluoric acid.
• Another object of the present invention is to provide a process which achieves high conversion yields and reaction yields.
• Another object of the present invention is to provide a process of the above type which makes it possible to avoid the release, or at least to limit the release, of fluorophosgene.
• HF + exchangeable halogen carbamoyl fluorides (s) + isocyanate + carbamoyl fluorides this report relates to all the species contained in the reactor, whether they are in the gas phase or that they are in liquid phase (s). If, in the case where one works in an open (not closed) reactor, the quantity of HF in the gas phase is not easily determinable, only HF in the liquid phase (s) will be taken into account.
• exchangeable halogens heavier than fluorine, carried by the halogen-bearing carbon (s)
• exchangeable halogens are those which can be exchanged by the action of liquid hydrofluoric acid in large excess (more than 4 times the stoichiometry) under autogenous pressure at a temperature of 100 ° C for 10 hours].
• the invention relates above all to light substrates whose carbon number is at most 50, advantageously at most 30, preferably at most 20 carbon atoms.
• s carbamoyl fluoride
• the sum of the Hammett constants ⁇ p is at least equal to 0.2; preferably 0.4; preferably 0.7.
• the entire exchange does not necessarily take place at elevated temperatures (at least equal to 70 ° C.), only the part of the reaction where the ratio Q ′ is less than 0.8, of preferably 1, should advantageously take place at these high temperatures.
• solvents whose boiling point (starting, in the case of mixing) under atmospheric pressure, that is to say at least 100 ° C, advantageously at least 120 ° C.
• the solvents should also be chosen so that they are easily separable from the substrate and from the final product.
• the solvents which give good results are often those which are at least partially miscible with hydrofluoric acid, and in particular among the halogenated aromatic derivatives not reactive with carbamoyl fluoride.
• the solvents are aromatics, it is desirable that their core (s) is (are) deactivated (s) to avoid parasitic reactions between the initial substrate and the solvent, and this especially when, according to one of the modes
• a catalyst based on Lewis acid is used.
• the active constituent of the catalyst is chosen from Lewis acids and mixtures of Lewis acids. Most often I use only one Lewis acid.
• the present invention is especially of interest when the carbamoyl fluoride used as fluorination agent is formed from the starting substrate which then comprises both an isocyanate function and a function carrying halogen atoms to be exchanged with fluorine.
• the carbamoyl fluoride (s) which will be used for halogenation, more precisely for fluorination by halogen exchange in situ; that is to say that is introduced into the medium containing the isocyanates, initial, formed as reaction intermediate or formed as final product obtained by addition of gaseous hydrofluoric acid.
• the isocyanates are aromatic isocyanates, that is to say isocyanates linked directly to an aromatic nucleus.
• the substrate comprises a halogenating carbon sp 3 hybridization carrying at least two halogens, at least one of which is a halogen with an atomic number greater than that of fluorine, which halogenating carbon is linked to at least one weak hybridization atom carrying an unsaturation or linked to an atom carrying a doublet capable of activating said halogenophore carbon under the operating conditions of the process.
• Said atoms carrying doublets are advantageously chalcogens.
• the effect of the chalcogen is stronger the higher it is, so the sulfur is a chalcogen more efficient than oxygen from the point of view of the activation of the carbon halogenophore.
• the halogenophore carbon advantageously corresponds to the formula -CX ⁇ - GEA where Xi and X 2 represent halogens, similar or different, and the radical GEA represents a halogen or group which represents a hydrocarbon group, advantageously an electron-withdrawing group X 3 (constant sigma index p of Hammett greater than 0); with the condition that at least one, advantageously two of the ⁇ X 2 , and GEA are halogen different from fluorine; the dash indicating the free bond connecting the halogenophore carbon to the radical activating X ⁇ X 2 and X 3 being defined later.
• said atom, of weak hybridization, carrying an unsaturation is engaged in a carbon-carbon bond (acetylenic, preferably ethylenic, which ethylenic bond is itself advantageously engaged in an aromatic ring), indicate by way of teaching by example that, advantageously, said atom, of weak hybridization, carrying an unsaturation is an atom engaged in one of the double bonds [where * C is the halogenophore carbon] following:
• the reaction is all the easier when the halogens carried by the aliphatic halogenophobic carbon, that is to say sp 3 hybridization, have little fluorine, and it is all the easier as the proportion of isocyanate is high in the reaction mixture.
• the reaction, object of the present, can be used either to make a selective exchange by leaving the last halogen heavier than fluorine on the carbon halogenophore, or especially to carry out a complete exchange by limiting the excess of hydrofluoric acid.
• the reaction in particular when there are several exchanges to be carried out, can be carried out in several stages or in several stages.
• the first exchange (s) (one or two exchanges) are carried out cold, that is to say at a temperature below 60 ° C, advantageously at 50 ° C, preferably at 40 ° C, more preferably at 30 ° C, and in a second step the exchange complete is obtained by heating to a temperature at least equal to 70 ° C., advantageously 90 ° C.
• the reaction can easily be carried out continuously in a cascade of reactors whose temperatures meet the above conditions, in co- or counter-current.
• the use of piston reactor may be considered.
• the catalyst can be present in a molar ratio (catalyst / substrate) of 1% 0 to 20%. If the catalyst is present throughout the exchange, it is preferable to limit its presence to a molar ratio value at most equal to 0.1; or even at most 5%; advantageously from 0.5 to 5%; preferably 1 to 3%. If we limit the use of the catalyst to the part of the process higher than 70 ° C, or to the last heavy halogen of the halogenophore carbon, which can be designated by last exchange, we can place sacred in the upper part of the range, that is to say a presence in a molar ratio of 1 to 20%.
• the catalyst (s) are introduced into the mixture in the form of heavy halides, for the calculation of the ratios specified above, it will be considered, before the calculation, that all the heavy halides of the catalyst will have been displaced by the fluoride of the hydrofluoric acid, the part of hydrofluoric acid having served to displace said heavy halides from the catalyst no longer available for exchange.
• the most useful catalysts are the antimony V, tin IV, tantalum and titanium IV salts. Antimony and especially tin are preferred. Titanium also provides excellent results. These salts can be used alone or in mixtures. Most often, because the most practical, the salts of a single element are used as catalyst.
• the reaction is all the more interesting as the substrate and the carbamoyl fluoride belong to the same line of reaction intermediates.
• said carbamoyl fluoride comprises an aliphatic carbon, that is to say sp 3 hybridization, carrying at least two halogens of which advantageously at least one, preferably two are fluorine.
• said aliphatic carbon carrying one or more fluorines is advantageously benzyl, that is to say that it is directly attached to an aromatic nucleus, this said aromatic nucleus advantageously being the one which carries the carbamoyl function nitrogen; in other words when you are faced with a compound having two aromatic rings, it is preferable that the halogenophore carbon atom is carried by the same aromatic ring as that which carries the nitrogen of the carbamoyl function or of the isocyanate function.
• ⁇ Ar is an aromatic ring, advantageously six-membered, preferably homocyclic; a the X, similar or different, represent a fluorine or a radical of formula C n F 2n + 1 , with n integer at most equal to 5, preferably 2; D p represents an integer at most equal to 2; ⁇ GEA represents a hydrocarbon group, an electron-withdrawing group whose any functions are inert under the reaction conditions, advantageously fluorine or a perfluorinated residue of formula C n F 2n + 1 , with an integer at most equal to 8, advantageously 5; the total number of carbons of - (CX 2 ) P -GEA is advantageously between 1 and 15, preferably between 1 and 10; ⁇ m is 0 or an integer chosen from the closed interval (that is to say comprising the limits) 1 to 4, advantageously m is at most equal to 2;
• Q Z represents a single bond or a chalcogen atom D X 1 ( and X 2 represent halogens, similar or different, with the condition that at least one, advantageously two halogens are different from fluorine; ° Ri and R 2 are substituents among halogens, alkyls, aryls, nitriles; ⁇ the radical X 3 is a halogen or electron-withdrawing group (sigma constant index p greater than 0) which does not interfere with the reaction and, in particular, may be a perfluorinated group, generally designated in the field of technology by " R f "; with the condition that at least one, advantageously two of X ⁇ Xs and X 3 are halogen different from fluorine.
• chlorobenzenes in particular monochloro, dichloro, trichlorobenzene and their mixtures.
• the reaction is advantageously stopped only when there is no more than 1 halogen atom to be exchanged out of 100 initially present, preferably only 1% of molecules carrying at least one atom remaining of halogen to be exchanged.
• the first reaction is the addition of hydrofluoric acid to the isocyanate to form carbamoyl fluoride.
• Chlorobenzene loading then the autoclave is closed, cooled to 0 ° C. With stirring is introduced at 0 ° C THF.
• the autoclave is equipped with a weir to regulate the pressure. The pressure is regulated to 2/3 bars, the reaction medium is heated to 10 ° C, the pTCMI is then introduced in approximately 10 minutes, the reaction medium is then heated to 25 ° C under 2.5 bar, for 7 h.
• the reactor is degassed at 25 ° C (weir opening) and then cooled to 0 ° C overnight.
• the reaction medium is heated to 120 ° C. under autogenous pressure for 6 h (end of test pressure 9.4 bar).
• the analyzes are carried out by gas chromatography (GC).
• the reaction medium is heated to 120 ° C under autogenous pressure for 6 h.
• reaction mass is diluted with methylene chloride and then washed quickly with water
• TFMB trifluoromethylbenzene TCB; trichlorobenzene
• reaction mass is cooled, residual THF is eliminated by bubbling nitrogen through - the reaction mass is diluted with methylene chloride and then washed quickly with water
• the yield is determined by GPC analysis (the carbamoyl fluoride from pTFMI and pTFMI are not separated).
• the pTFMI / carbamoyl fluoride composition of pTFMI is determined by infrared analysis.

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• 2002
  • 2002-01-10 HU HU0302628A patent/HUP0302628A3/hu unknown
  • 2002-01-10 US US10/450,600 patent/US6833476B2/en not_active Expired - Fee Related
  • 2002-01-10 EP EP02711937A patent/EP1349831A2/de not_active Withdrawn
  • 2002-01-10 WO PCT/FR2002/000075 patent/WO2002055487A2/fr active Application Filing
  • 2002-01-10 CN CNB028035976A patent/CN100554248C/zh not_active Expired - Fee Related
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• 2010
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