IE65876B1 - Preparation of a perfluoroalkyl bromide by photobromination of the corresponding iodide - Google Patents

Abstract

The invention relates to the manufacture of a perfluoroalkyl bromide RFBr by photochemical bromination of the corresponding iodide RFI. In order to obtain a virtually complete conversion of the RFI, its photobromination is carried out in solution in a solvent, the concentration of RFI being no more than 0.5 mol/litre.

Description

The present invention relates to the preparation of bromides of the formula RFBr, RF denoting a linear or branched r perfluoroalkyl radical containing from 2 to 14 carbon atoms, and in particular to the preparation of n-perfluorooctyl * bromide C8F17Br (hereinafter denoted by the abbreviation PFOB) .

It is known that the compounds RFBr and more particularly PFOB show very interesting properties for use in the medical field as contrast agents (radiology) or as oxygen carriers (artificial blood). The future development of these compounds in such applications seems to be considerable. It is therefore necessary to be in a position to produce them industrially by an economic method with a very high purity.

Among the known methods for preparing the compounds RFBr, there may first be mentioned: - the action of bromine on a compound RfSF5 at 500°C in the presence of nickel (US Patent 3,456,024); - the gas-phase photolysis of a compound RFH by Br-Cl or Br-F (J.L. Adcock et al, CA 100. 34092 e) or by Br2 (French Patent FR 1,512,068).

The low yields obtained, and/or the use of fluorinated derivatives which are not available industrially, do not allow economic production of the compounds RFBr on the industrial scale.

European Patent EP 0,298,870 and European Patent , Application EP 90403118.4 describe methods of manufacture of compounds RFBr from the corresponding perfluoroalkanesulphonyl chlorides RFSO2C1 which are made to react either with gaseous HBr in the presence of a catalyst (EP 0,298,870) or with a quaternary ammonium or phosphonium bromide (EP 90403118.4). The yields obtained are generally high, but the sulphochloride RFSO2C1 used as starting material is already very complex, since its synthesis from the corresponding iodide RFI requires two reaction stages according to the equation: Zn 2C12 RfI + 2 SO2 -► (RFSO2)2Zn -> 2 RFSO2C1 + ZnCl2 The most direct way of obtaining the compounds RFBr would be a radical bromination of the corresponding iodides RfI, the latter being products which are available in industrial quantities.

International Journal of Chemical Kinetics, Vol. II, 273-285 (1975), E.N. Okafo and E. Whittle, describes the kinetics of thermal bromination of CF3I in a photochemical reactor at between 173 and 321°C, for the purpose of determining the dissociation energy of the C-I bond.

J. Chem. Soc. 1953, 3761-8, R.N. Haszeldine, describes a photochemical method of reaction of the RFI compounds with bromine in a sealed tube with an excess of bromine (10 %) and while irradiating with UV light for seven days. The reaction temperature and the purity obtained are not specified; it is simply indicated that the yield is higher than or equal to 90 % according to the length of the perfluorinated chain RF.

In the examples in Japanese Application Kokai 854 184033, which describes the reaction of the compounds RFI with Br2 in the presence of a chemical radical initiator, the yields indicated do not exceed 42 %.

The low yields obtained and/or the slow kinetics of these techniques, as well as the incomplete transformation of the RFI, do not allow industrial exploitation to be envisaged. Indeed, taking account of the target applications (medical field) the compounds RFBr, and more specifically PFOB, must show a high purity, in particular a very low content of iodides RFI, which are unstable with time and develop a pink coloration and which are difficult to separate by distillation, their boiling point being close to that of the corresponding bromide.

Moreover, it has been noted that, if the photobromination of an RFI is carried out according to the conventional technique, that is to say by introducing the RFI and an excess of Br2 into a photochemical reactor equipped with a lamp emitting at wavelengths between 300 and 650 nm, the RfI is transformed into RFBr with quite rapid kinetics at the beginning, then the speed of the reaction diminishes very rapidly and stops at an overall degree of transformation lower than 20 %.

It has now been found that it is nevertheless possible to photochemically brominate a perfluoroalkyl iodide RFI to RFBr with a very high quantitative conversion if the photobromination is carried out in dilute medium using as a solvent of the RFI either the RFBr compound itself or an inert solvent such as, for example, CC14 or C2F3C13.

According to the present invention there is provided a method of preparing a perfluoroalkyl bromide of formula RFBr 4 by photochemical bromination of the corresponding iodide RFI, characterised in that a solution of the RFI in a solvent is subjected to the photobromination, the concentration of RFI in the said solution being at roost 0.5 mol/litre.

The solubility of the RFI in the solvent (preferably RFBr) is generally very much higher than 0.5 mol/litre, but experiments carried out have shown that its concentration in the solution subjected to the photobromination must not exceed this value in order to obtain a substantially complete conversion of the iodide RFI. For the kinetics of the reaction, it is moreover preferable to use a concentration of RfI lower than 0.35 mol/litre and, advantageously, lower than 0.2 mol/litre.

The starting solution can be prepared simply by mixing the RfI and the solvent, but it is also possible to use the product obtained by careful thermal bromination of the iodide RfI, it being possible, where appropriate, for this product to be diluted by addition of RFBr in order to bring it to the desired concentration of RfI.

The photobromination can be carried out noncontinuously or continuously, in a photochemical reactor,, for example in an immersion or a falling film photoreactor, Λ equipped with a lamp envelope of quartz or pyrex and equipped with a lamp emitting at wavelengths between 300 and 650 nm.

The bromine is preferably introduced progressively so as to completely absorb the light. The total quantity of bromine to be used is at least one mole per mole of RFI present in the initial solution, but a bromine excess of 10 to 100 %, in particular around 25 %, is preferably used.

The photobromination according to the invention can be suitably conducted at a temperature of between 10°C and the boiling point of the solvent, but is preferably carried out at between 15 and 50°C. The operation is advantageously carried out at atmospheric pressure, but it would not be beyond the scope of the present invention to work under slight pressure or vacuum.

The method according to the invention applies both to the preparation of a specific RFBr (for example, C6F13Br, C8F17Br, C10F21Br) and to that of a mixture of different RFBr compounds from a mixture of the corresponding RFI compounds.

The Examples which follow further illustrate the invention. In order to follow the progress of the reaction with time, samples are removed and, after reduction and removal of the free iodine and bromine, they are analysed by gas phase chromatography (thermal conductivity detector). The overall degree of transformation (DT0) of the RFI is calculated from the following formula: % DT0 100 X (1 initial RFI - residual RFI initial RFI Since the detection limit of the apparatus is around 1000 ppm for RfI, a DT0 of 100 % is considered to have been obtained when this detection limit is reached.

EXAMPLE 1 (Comparative) Into an immersion photochemical reactor with a capacity of 150 ml, equipped with a Philips HPK 125 lamp and a magnetic stirrer, are charged 270 g (140 ml) of perfluorooctyl iodide (purity > 99.5 %) and then this compound is irradiated at 30 ± 2°C while introducing bromine, this introduction being carried out dropwise in such a manner that the absorption of the bromine is total.

After irradiating for 24 hours, a sample (2 ml) is withdrawn and is treated with an aqueous solution of sodium sulphite. Its GPC analysis shows that the PFOB (C8F17Br) content is 12.5 % by weight, which corresponds to a DT0 of 13.5 %.

The irradiating of the reaction mixture is continued for a further 15 hours at 55°C. GPC analysis of the crude reaction mixture then shows a PFOB content of 18.7 % by weight, that is to say a DT0 of only 20.1 %.

EXAMPLE 2 Into the same apparatus as in Example 1 are charged 140 ml of a solution of 10 g (18.3 millimoles), of perfluorooctyl iodide in PFOB (that is to say, a molar concentration of C8F17I of 0.13 mol/litre) .

This solution is then irradiated at 15-20°C while introducing bromine dropwise. After irradiating for 18 hours, the C8F17I concentration in the crude reaction mixture has f become less than the detection limit (0.1 %). The DT0 is considered as being equal to 100 %.

EXAMPLES 3 TO 5 Example 2 is repeated while varying the quantity of C8F17I dissolved in the PFOB, namely: - 6 g for Example 3 - 25 g for Example 4 - 50 g for Example 5 (comparative) the volume of solution remaining the same (140 ml).

In Examples 3 and 4, a DT0 of 100 % is obtained after irradiating for respectively 12 hours and 49 hours. In the case of Example 5, the DT0 reaches a maximum at 75 % after irradiating for 50 hours.

The following table summarises the results from the previous Examples 1 to 5.

EXAMPLE C8F17I in % by weight PP0B(a) mol/litre Length of irradiation (hours) Residual C0fi7I (% by wei< DT0 :jht) % 1 Canpara ;ive 100 3.5439(b) 81.3 20.1 2 3.7 0.13 18 < 0.1 100 3 2.2 0.08 12 < 0.1 100 4 9.25 0.33 33 49 0.2 < 0.1 98 100 5 Canpara· 1 18.5 tive _ 0.66 33 50 5.6 4.7 70 75 (a) No PFOB in Exanple 1 (b) 24 hours at 30°C, then 15 hours at 55°C EXAMPLE 6 The procedure is as in Example 2, but using as the initial solution a product obtained beforehand by thermal bromination of C8F17I. This product contains 12.45 % by weight of residual C8F17I, which corresponds to a molar concentration of 0.44 mol/litre.

After irradiating for 23 hours at 15-20°C, the C8F17I content is now only 6 %. It is lower than 0. l % after irradiating for 60 hours (DT0 = 100 %) .

EXAMPLE 7 Into a falling film photochemical reactor with a capacity of 1600 ml, equipped with a 720 watt HANAU TQ 718 lamp and with an external recirculation pump, are charged 1400 ml of a solution of 250 g (0.46 mol) of C8F17I in PFOB (that is, a molar concentration of 0.33 mol/litre). c This solution is irradiated at 15-20°C under circulation, while introducing bromine therein dropwise, the A total quantity of bromine corresponding to a 25 % excess in relation to the stoichiometry.

After irradiating for 48 hours, GPC analysis shows a residual C8F17I content of 5.5 % by weight. It is now only 0.28 % after irradiating for 200 hours (DT0 = 97 %) .

By comparison, when starting from 1400 ml of pure C8F17I, the test must be stopped after irradiating for 62 hours due to a precipitation of I2 and IBr which impedes the effective working of the recirculation pump. GPC analysis then shows a PFOB content of 26 % by weight (that is, a DT0 of 27.7 %).

EXAMPLE 8 Into the same apparatus as in Example 1, are charged 140 ml of a solution of 25 g (56 millimoles) of nperfluorohexyl iodide in n-perfluorohexyl bromide, then this solution is irradiated at about 20°C while introducing bromine dropwise.

After irradiating for 48 hours, the residual C6F13I content of the crude reaction mixture has become lower than the detection limit of 0.1 % (DT0 = 100 %).

EXAMPLES 9 AND 10 Into the same apparatus as in Example 1 are charged 140 ml of a solution containing 15 g of C8F17I in carbon tetrachloride (Example 9) or in 1,1,2-trichloro-1,2,2trifluoroethane (Example 10).

The irradiation (24 hours) is carried out at about 5 20°C while introducing bromine dropwise. The results obtained are summarised in the following table.

EXAMPLE Solvent (% by weight) Residual C8F17I % DT0 9 cci4 < 0.1 100 10 C2F3Cl3 < 0.1 100

Claims (13)

1. A method of preparing a bromide of the formula R F Br, where R F represents a linear or branched perfluoroalkyl radical containing from 2 to 14 carbon atoms, which method comprises subjecting to photobromination the corresponding perfluoroalkyl iodide of the formula R F I in which R F is as defined above, the R F I being subjected to the photobromination in a solution in a solvent and the concentration of R F I in the said solution being at most 0.5 mol/litre.

2. A method according to Claim 1, in which the concentration of R F I is below 0.35 mol/litre.

3. A method according to claim 1, in which the concentration of R F I is below 0.2 mol/litre.

4. A method according to any preceding claim, in which the solvent used is the R F Br itself.

5. A method according to Claim 4, in which the initial solution of R F I in the R f Br is obtained by thermal bromination of the R F I.

6. A method according to any one of claims 1 to 3, in which the solvent used is carbon tetrachloride or 1,1,2trichloro-1,2,2-trifluoroethane.

7. A method according to any preceding claim, in which a total of 1.1 to 2 moles of bromine per mole of R F I present in the initial solution is used.

8. A method according to any preceding claim, in which the photobromination is carried out at atmospheric pressure and at a temperature of between 15 and 50 °C.

9. A method according to any preceding claim for the preparation of n-perfluorooctyl bromide.

10. A method according to any one of claims 1 to 8 for the preparation of n-perfluorohexyl bromide. 5

11. A method according to any one of claims l to 8 for the preparation of a mixture of perfluoroalkyl bromides.

12. A method according to claim 1 substantially as described in any one of Examples 2 to 4 and 6 to 10.

13. A bromide of the formula R F Br (in which R F is as 10 defined in claim 1) prepared by the method claimed in any one of claims 1 to 12.