JP2819501B2 - Method for producing mostly fluoroalkyl bromides - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the preparation of predominantly fluorinated alkyl bromides, in particular perfluoroalkyl bromides, starting from predominantly fluorinated alkyl iodides, in particular power fluoroalkyl iodides. It relates to a manufacturing method.

Mostly fluorinated alkyl bromides, in particular perfluoroalkyl bromides, for example as intermediates for the preparation of polymer liquids, resins and elastomers, as radiographic contrast agents, for the preparation of pharmaceutical preparations,
And in the form of an aqueous emulsion as a blood substitute. A preferred fluoroalkyl bromide as a blood substitute is perfluorooctyl bromide.

A series of processes are already known for the production of perfluoroalkyl bromides. For example, JP-A-61-1840
No. 33, CA Vol. 104 ((1986), 88106p), perfluoroalkyl iodide is reacted with elemental bromine in the presence of a radical initiator to form perfluoroalkyl bromide. J. Chem. Soc. 1953 , 3761
-3768), p. 3763 and p. 3766, describe the reaction of perfluoroalkyl iodide with elemental bromine under UV-light irradiation. Two methods are:
The use of elemental bromine leads to significant material and technical safety issues due to the release of elemental iodine, halogen endogenous compounds and hydrogen fluoride.

Other manufacturing methods for perfluoroalkyl Pro bromide are, for example, the following (R _F = perfluoroalkyl) to act in the presence of nickel bromine 500 ° C. to the compound R _F -SF ₅ (U.S. Patent No. 3456024); the action of bromine on the compound R _F -SO ₂ Na in the presence of KI / I ₂ (CA
107 (987), 236043); acting bromine on perfluorinated carboxylic acid salts (US Pat. No. 2,679,953), especially on R _F COOAg (US Pat. No. 26789)
No. 53 and Hauptschein,
. J.Am.Chem.Soc 74 (1952), see below pp 1347); to act simultaneously irradiating bromine with a compound R _F H to UV- light (J.Che
m.Soc.1953,3761). In all this case, the use of elemental bromine creates significant material and technical safety issues. Furthermore, the starting compounds are difficult to obtain or have to be prepared from the corresponding perfluoroalkyl iodides via additional processing steps. This means that perfluoroalkyl bromide can be converted to R _F SO ₃ Cl and HBr-
The same applies to the production by reacting a gas at 125 ° C. in the presence of a catalyst (EP-A-0 298 870).

Fan Berg (Fainberg), etc., JACS 79 .1472 (195
According to 7), perfluoroallyl bromide can be produced by reacting perfluoroallyl iodide and lithium bromide in acetone.
The apparent diversion of this halogen exchange to other perfluoroalkyl iodides does not work. This is because there is no activation of iodine by allyl groups in normal perfluoroalkyl iodides. As is apparent from Comparative Example 1 below, the reaction conditions described by Vanberg et al. Do not apply effectively to perfluorooctyl iodide. Comparative Examples 2 and 3 below show that kinetic experiments under phase transfer-catalysis do not give satisfactory results.

The comparative example corresponds to the possibility in the result. This is because it is known that a fluorine atom apparently passes the reactivity of an alkyl halide in a nucleophilic substitution reaction. (See, for example, Houben-Wale, Methods of Organic Chemistry, 4th Edition, Vol. 5/4, p. 685, p. 688).

Conventionally known methods of predominantly fluoroalkyl bromides and of the perfluoroalkyl bromide disclosed in Japanese Patent Application Laid-Open (JP-A) no. The object of the present invention was therefore to start from readily available mostly fluorinated alkyl iodides, in particular perfluoroalkyl iodides, and to predominantly fluorinated alkyl bromides, The use of a technically simple process for the preparation of orthoalkyl bromides.

Surprisingly, the present inventors have found that when using equimolar amounts of the phase transfer catalyst present in the form of the bromide, the predominantly fluorinated alkyl bromides, preferably perfluoroalkyl bromides, are handled in simple reactions. Has been found to be available from fluorinated alkyl iodides, preferably perfluoroalkyl iodides.

The present invention relates to a process for the preparation of predominantly fluorinated alkyl bromides, starting from predominantly fluorinated alkyl iodides. The process according to the invention is characterized in that the mostly fluorinated alkyl iodides are reacted with the phase transfer catalyst present in the form of bromide in a molar ratio of 1: (0.4 to 3).

"Predominantly fluorinated" means that, in addition to the bromine or iodine atom in the alkyl bromide or alkyl iodide, there is mainly one or only a few, preferably hydrogen atoms, of hydrogen and hydrogen atoms. . The process according to the invention, especially formula _{I X-C n F 2n -Br} (I) wherein X = H, F or (F ₃ C) ₂ CF- and n is 1 to 20,
It is suitable for the preparation of alkyl bromides which are predominantly fluorinated, preferably representing 4 to 16, particularly preferably 6 to 12. Wherein group -C in I _n H _2n -, especially - (CF _{2) n} - form a (II) made form. In order to produce predominantly fluorinated alkyl bromides according to the process according to the invention,
Mostly use fluorinated alkyl iodides. This is a compound which differs from the desired end product only by replacing bromine with iodine. Therefore the formula _{III X-C n F 2n -I} (III) wherein X as the starting compound in the process according to the present invention, n and C _n F _2n have the abovementioned meanings, are preferably used comprising compound.

At a Formula I and III, X is preferably (F _{3 C)} 2 -CF-
And particularly preferably F. The process according to the invention is therefore particularly suitable for the preparation of perfluoroalkyl bromides, particularly preferably those having 6 to 12 C atoms, more particularly preferably for the preparation of perfluorooctyl bromide.

The mostly fluoroalkyl iodides used as starting compounds, in particular the compounds of the formula III, are known or can be prepared according to various methods known in this class of compounds.

All organic compounds can be used as phase transfer catalysts, in which bromine is present in anionic form, which compound has sufficient solubility in the reaction catalyst. Suitable phase transfer catalysts are in particular bromides of quaternary organic compounds, such as the general formulas IV, V and VI: Quaternary ammonium-, phosphonium- and arsonium compounds.

In such a phase transfer catalyst, the four residues R may represent the same or different and / or functional groups. The residue R can be, for example, an alkyl group having 1 to 20 C atoms, phenyl- or benzyl group. Central onium-
In addition to nitrogen, phosphorus and arsenic as atoms, other atoms such as antimony or sulfur can be mentioned. Suitable phase transfer catalysts are, for example: (CH ₃ ) ₄ NBr, (C ₂ H ₅ ) ₄ NBr; (C ₄ H ₇ ) ₄ NBr; (C ₄ H ₉ ) ₄ NB
r; (C ₈ H ₁₇ ) ₃ NCH ₃ Br; C ₆ H ₅ CH ₂ N (C ₂ H ₅ ) ₂ Br; C ₆ H ₁₃ N (C ₂ H
₅ ) ₃ Br; C ₈ H ₁₇ N (C ₂ H ₅ ) ₃ Br; C ₁₀ H ₂₁ N (C ₂ H ₅ ) ₃ Br; C ₁₂ H ₂₅
N (C ₂ H ₅ ) ₃ Br; C ₁₆ H ₃₃ N (CH ₃ ) ₃ Br; C ₁₆ H ₃₃ N (C ₂ H ₅ ) ₃ Br;
(C ₆ H ₅ ) ₄ PBr; (C ₆ H ₅ ) ₃ PCH ₃ Br; (C ₈ H ₁₇ ) ₃ PC ₂ H ₅ Br; C ₁₆
Preference is given to using H ₃₃ P (C ₂ H ₅ ) ₃ Br. Quaternary ammonium- or phosphonium-bromide. Particularly preferred are quaternary phosphonium bromides, especially tetraalkylphosphonium bromides, wherein the individual alkyl groups have 1 to 20 C-atoms,
For example, tetrabutylphosphonium bromide. Mixtures of various phase transfer catalysts can also be used.

The preparation of said phase transfer catalyst is known. Many are commercially available.

The reaction according to the invention is carried out by simple mixing of a predominantly fluorinated alkyl iodide with a phase transfer catalyst. No addition of solvent is necessary. However, the reaction can also be carried out in a suitable solvent or solvent mixture.

Use a phase transfer catalyst that is sufficient to provide sufficient conversion per mole of predominantly fluorinated alkyl iodide. Mostly fluorinated alkyl iodides
It is preferred to use from 0.4 to 3 mol, preferably from 0.5 to 2 mol, and particularly preferably from 0.8 to 1.4 mol, of the phase transfer catalyst per mole in bromide form. In most cases, the molar ratio is predominantly fluoroalkylsodide: phase transfer catalyst = 1: 1 or about 1: 1.

It is also possible to use more than 3 moles of phase transfer catalyst per mole of mostly prefluorinated alkyl iodide. But this does not bring any advantage. With too little phase transfer catalyst, insufficient conversion is obtained.

The phase transfer catalyst can also be used as a solid or in the form of an aqueous liquid. The water is then distilled from the reaction mixture before the actual reaction. This distillation of water is conveniently effected azeotropically, returning the organic phase to the reaction mixture.

The reaction temperature is between 0 ° C. and the boiling point of the reaction mixture under normal pressure. The reaction is carried out under normal pressure, in particular at a temperature between 20 ° C. and the boiling point of the reaction mixture, preferably at normal temperature up to the boiling point of the mostly fluorinated alkyl iodides. In many cases, the reaction is carried out at a temperature between 50 and 140 ° C. Reaction rates are usually higher at higher temperatures than at lower temperatures.

The reaction is preferably carried out under an inert gas atmosphere, for example under argon.

The reaction or work-up can be carried out in various ways, for example by distilling the largely fluorinated alkylfuromide formed during or after the reaction. After the reaction, the temperature of the reaction mixture is optionally reduced, water is added to the reaction mixture, i.e., it is mixed well, after which the mixture is separated into an aqueous and an organic phase, and the separated organic phase is distilled into its components, i.e. Work-up can be performed such that the predominantly fluorinated alkyl bromide and the largely unreacted fluorinated alkyl iodide are separated. The compound of the invention recovered in this post-treatment can be newly supplied to the reaction.

The phase transfer catalyst present as an iodide / bromide mixture after the end of the reaction can be informed back into pure bromide again. With the preferred work-up of the reaction mixture (water added to the reaction mixture, phase separation), the remaining aqueous phase contains the phase transfer catalyst as an iodide / bromide mixture.

To convert the iodine moiety to bromide form, the aqueous phase
Commit to an ion exchanger that converts iodide to bromide. Suitable ion exchanger polymers are known. The aqueous solution of the phase transfer catalyst produced by ion exchange is
As mentioned above, it can be used directly in the reaction according to the invention. However, it is also possible to isolate the aqueous solution of the phase transfer catalyst as a solid, which is then used fresh for carrying out the reaction according to the invention.

In the process according to the invention, the desired largely fluorinated alkyl bromides, preferably perfluoroalkyl bromides, are obtained in a yield of more than 99% (relative to the reacted starting compounds). Unreacted starting compounds can be recovered in a simple manner and used fresh. The phase transfer catalyst in the form of a bromide is used not as a catalyst in the reaction according to the invention, but as a reactant and is largely converted to the corresponding iodide form in the reaction. The iodide form can easily be converted back to the bromide form and then used again. The purity of the final product produced, as determined by gas chromatography, is high, often above 99%.

 The invention is further described by the following examples.

Example 1 986 g perfluorooctyl iodide (1.81 mol) and 613 g tetrabutylphosphonium bromide (1.81 mol)
Is refluxed for 8 hours.

Up to 160 ° C pool temperature, then gradually 140-143 ° C
Distill perfluorooctyl bromide at the top temperature. The reaction mixture is then distilled again at reduced pressure (18 mbar).

After cooling to 90 ° C., 250 ml of water is added to the pool, and unreacted perfluorooctyl iodide is azeotropically distilled. After phase separation, the distillates were combined, washed with sodium disulfite,
Then, fractional distillation is performed.

Yield: 540 g perfluorooctyl bromide, 340 g perfluorooctyl iodide, which is 60% of the theoretical value or 91% of the theoretical value for unreacted perfluorooctyl iodide.

Boiling point: 142-143 ° C. GC: Purity greater than 99% 500 g of the remaining residue are dissolved in a total of 4500 g 20% methanol, thoroughly stirred with 5 g activated carbon, filtered,
Suitable for regeneration of polymer ion exchange resin.

Example 2 Example 1 is repeated, but using tetrabutylphosphonium bromide in the form of an aqueous solution. Before the actual reaction, the water is distilled off azeotropically with the return of the organic phase. The reaction mixture is then
Heat to 140 ° C. for time, cool to room temperature and mix with 500 ml water. The phases are separated, the organic phase is washed with sodium disulphite and then fractionally distilled.

Yield: 530 g perfluorooctyl bromide, 345 g perfluorooctyl iodide, which is 58% of the theoretical value or 90% of the theoretical value for unreacted perfluorooctyl iodide.

Boiling point: 142-143 ° C GC: Purity greater than 99% The following comparative examples are based on JACS such as Fainberg.
S 79, 4172 by (1957) show that the reaction conditions described for the preparation of par fluoroalkyl allyl bromide can not be diverted to the production of par-fluorobenzyl bromide. Comparative Examples 2 and 3 below show that performing the reaction under phase transfer conditions does not result in an effective yield of perfluorooctyl bromide.

Comparative Example 1 100 g of perfluorooctyl iodide (183 mmol) was added within 10 minutes to a solution containing 19 g (LiBr (220 mmol) in 150 ml of dry acetone, followed by boiling for 8 hours under reflux.
Pour into 00 ml water, separate the organic phase and dry with a small amount of CaCl ₂ .

Yield: 100 g perfluorooctyl iodide 95%.

Perfluorooctyl bromide is not detectable by gas chromatography.

Comparative Example 2 100 g perfluorooctyl iodide (183 mmol), 7
5 g CaBr ₂ (375 mmol), 25 ml water and 1 g tetrabutylammonium bromide (1.5 mol%) are boiled under reflux for 5 hours. Pour into 500 ml water, separate the organic phase, wash the organic phase free of halogenides and dry with a small amount of CaCl ₂ .

Yield: 94 g GC: 1% perfluorooctyl bromide, 96% perfluorooctyl iodide.

Comparative Example 3 As in Comparative Example 2, 1 g tetrabutylphosphonium bromide (1.5 mol%) is obtained as phase transfer catalyst: Yield: 95 g GC: 1% perfluorooctyl bromide 97% perfluorooctyl iodide

──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Kneipps Reinhard, Germany, Day 3000, Hannover 91, Hermann-Ehrers-Alley, 20 (58) Fields investigated (Int. Cl. ⁶ , DB name) C07C 19 / 14,17 / 20

Claims (10)

(57) [Claims] 1. A phase-transfer catalyst which is predominantly present in the form of alkyl iodides and bromides in the preparation of predominantly fluorinated alkyl bromides starting from predominantly fluorinated alkyl iodides. And reacting at a molar ratio of 1: (0.4 to 3).
A method for producing the above compound. 2. A compound of the formula IX—C _n F _2n —Br (I) wherein XＦH, F or (F ₃ C) ₂ CF— and n are from 1 to 20,
And preferably contains 4 to 16, particularly preferably 6 to 12 are indicated, the majority of a fluorinated alkyl bromide production, formula III X-C _n F _2n -I as alkyl iodide which were largely a fluorinated Claim 1 characterized by using a compound (III)
The described method. 3. In the formulas I and III, the radical —C _n F _2n — is
(CF _{2) n} - has the form and (or) X is (F ₃ C) ₂ CF-,
Method according to claim 2, characterized in that it preferably has the meaning F. 4. A quaternary ammonium bromide or a quaternary phosphonium bromide as a phase transfer catalyst in the form of a bromide.
4. The method according to any one of items 1 to 3. 5. The process according to claim 1, wherein tetrabutylphosphonium bromide is used as a phase transfer catalyst in the form of bromide. 6. A phase-transfer catalyst in the form of mostly fluorinated alkyl iodides and bromides in a molar ratio of 1: (0.
5 to 2), preferably 1: (0.8 to 1.4), particularly preferably in a molar ratio of about 1: 1,
A method according to any one of claims 1 to 5. 7. The process as claimed in claim 1, wherein the reaction is carried out at a temperature of 20 ° C. (up to the boiling point of the reaction mixture, preferably at a temperature of 50 to 140 ° C.). Method. 8. After completion of the reaction, the reaction mixture is mixed with water,
8. A process as claimed in claim 1, wherein the mixture is then separated into aqueous and organic phases, and the organic phase is then separated by distillation into its components. 9. The work-up, in which the largely, fully fluorinated alkyl iodides recovered are used again as starting compounds and / or the iodide / bromide mixture of the phase-transfer catalyst resulting from the work-up is again treated with bromide. 9. The method according to claim 1, wherein the method is used again. 10. The process according to claim 1, wherein the process is used as perfluorinated alkyl iodide as perfluorooctyl iodide.