DD275078A1 - PROCESS FOR PREPARING PERFLUORIZED N-SUBSTITUTED DIMETHYL MORPHOLINES - Google Patents

Abstract

The invention relates to a process for the preparation of new perfluorinated N-substituted dimethylmorpholines. The new perfluoromorpholine derivatives of the general formula wherein AF is a perfluoroalkyl radical having 2 to 8 carbon atoms or a 5- to 7-membered perfluorinated ring, wherein in each case in the chain or in the ring, a carbon atom may also be replaced by oxygen or by a perfluoroalkylamino group, and BF stands for trifluoromethyl, are prepared by electrofluorination of the corresponding hydrogen-containing or partially fluorinated compounds. The new compounds can be used as aqueous emulsions for gas transport z. B. be used in medicine or biology. formula

Description

Λ - N Ü Il

\ A- B

in which A is an alkyl radical having 2 to 8 carbon atoms or a 5- to 7-membered saturated, unsaturated or aromatic ring, it also being possible for a carbon atom in the chain or in the ring to be replaced by an oxygen atom or by an alkylamino group, and B is methyl, which may already be teilfluoriert already be electrochemically perfluorinated in anhydrous liquid hydrogen fluoride on nickel anodes.

2. The method according to claim 1, characterized in that the perfluorinated alkyl radical Af preferably has 3-6 carbon atoms.

3. The method according to claim 1, characterized in that the perfluorinated cycloalkyl radical A _r preferably contains 5 to 6 carbon atoms.

4. The method according to claim 1, characterized in that Af is selected from the group consisting of propyl, butyl, pentyl, hexyl, heptyl, cyclohexyl, cyclopentyl and cycloheptyl, said groups being perfluorinated.

5. The method according to claim 4, characterized in that one produces porfluoro-4-butyl-2,6-dimethylmorpholine, perfluoro-cyclohexyl ^ .e-dimethylmorpholine, perfluoro-4-cyclohexyl-2,2-dimethylmorpholine.

Field of application of the invention

The invention relates to a process for the preparation of new perfluorinated r <imeihylsubstituierter morpholine derivatives. The perfluorinated Morpho'inderivate invention produced as inert and physiologically acceptable liquids in the form of their aqueous emulsion for Gastransportaufg. Ben, z. In medicine or biology.

Characteristic of the known state of the art

For the production of perfluorinated chemical compounds are oligomerization reactions, eg. For example, starting from tetrafluorothane, fluorination reactions with elemental fluorine and with higher-order metal fluorides and electrochemical fluorination reactions are used (see, for example, BREBanks (Ed.), Preparation, Properties and Industrial Applications of Organofluorine Compounds, Ellis Horwood Ltd., Chichester, UK, 1982). For the preparation of heteroatom-containing perfluorinated compounds, the electrochemical fluorination in liquid, anhydrous hydrogen fluoride, the so-called Simons process, is preferably suitable (see, for example, S.Nagase, Electrochemical Fluorination, Fluorine Chem. Rev. 1 (11.77-106 (1967)). By means of this process, it is possible to prepare heteroatom-containing perfluorocompounds from hydrogen-containing starting compounds whose molecular skeleton corresponds to that of the desired perfluoro compound, for example perfluorotributyinmine 2-tribrutylamine.

The preparation of perfluorinated N-substituted morpholine derivatives by means of electrochemical fluorination has previously been reported (eg, GPGambaretto, M.Napoli, C. Fraccaround L.Conte, J. Fluorine Chem. 19 (1982), 427-436, and S.A. Malkov, SIGerasimov, SV Sokolov and VL Zolotavin, Zh. Obs., Khim. 35 (1965) 485-489), but in all cases only N-substituted perfluorinated morpholines are described, but not N- and C-substituted.

Object of the invention

It is an object of the invention to provide novel heterocyclic perfluorinated compounds.

Explanation of the essence of the invention

The invention has for its object to develop processes for the preparation of new perfluorinated N-substituted dimethylmorpholines.

Perfluoromorpholine derivatives of general formula I are prepared according to the invention

wherein A _{F stands} for a perfluoroalkyl radical having 2 to 8 carbon atoms or for a 5- to 7-membered perfluorinated ring, wherein in each case a carbon atom may be replaced by an oxygen atom or by a Porfluoralkylaminogruppe, and B is CF ₃ .

Preferred compounds are those in which A _{f is} perfluoropropyl, -butyl, -pentyl-hexyl, -cyclopentyl or -cyclohexyl.

Most preferably, the compound is perfluoro-4-cyclohexyl-2,6-dimethylmorpholine.

Further preferred compounds according to the invention are:

Peifluoro-4-cyclohexyl-2,5-dimethylmorpholine 'perfluoro-4-cyclopentyl-2,6-dimethylmorpholine

Perfluoro-4-i; yclopentyl-2,5-dimethylmorpholine

Perfluoro 4cycloheptyl-2,6-dimethylrtiorpholin

Perfluoro-4-cycloheptyl-2,5-dimethylmorpholine

Per'luor-4-propyl-2,6-dimethylmorpho! In

Perfluoro-4-propyl-2,5-dimethylmorpholine

Perfluoro-4-butyl-2,6-dirr, ethylmorpholine

Perfluoro-4-butyl-2,5-dim * thylmorpholin

Perfluoro-4-pentyl-2,6-dimethylmorpholine

Perfluoro-4-phentyl-2,5-dimethylmorpholine

Perfluoro-4-hexyl-2,6-dimethylmorpholine

Perfluoro-4-hexyl-2,5-dimethylmorpholine

Perfluoro-4-heptyl-2,6-dimethylmorpholine

Perfluoro-4-heptyl-2,5-dimethylmorpholine

The new compounds can be prepared by electrochemical perforation in anhydrous, liquid hydrogen fluoride from morpholine derivatives of the general formula II

in which A is an alkyl radical having 2 to 8 carbon atoms or a 5- to 7-membered saturated, unsaturated or aromatic ring, it being also possible for a carbon atom to be replaced by an oxygen atom or by an alkylaminocide, B is methyl , The starting compounds may also already be partially fluorinated. The new N-substituted morphuline derivatives are inert and physiologically compatible compounds. In the form of aqueous emulsions they can be used for gastranoport in medicine (blood substitutes) and biology. The electrochemical fluorination is carried out in a Simons batch of nickel anodone in anhydrous liquid hydrogen fluoride boi 4.5V to 9V, preferably 5V to 8V, with current densities of 0.05A / dm ² to 8A / o'm ² . preferably at 0.1 A / dm ² to 3A / dm ² and at -2O ⁰ C to + 40 ¹ C, preferably carried out at 0 ° C to + 19'C. While the starting compounds are readily soluble in liquid hydrogen fluoride, the solutions have good electrical conductivity, the perfluorinated rVlorpholinderivate are not soluble in liquid hydrogen fluoride and deposit as a liquid, specifically schwerero soil phase. The resulting crude fluorination product is washed neutral with bicarbonate solution and distilled water, to woitoron cleaning os with 5 M KOH / dibutylamine (1: 1) refluxed for 5 days, washed neutral, treated with semi-concentrated sulfuric acid and washed neutral again. The purified perfluorocarbon mixture can be separated by distillation or a highly pure sample can be obtained by preparative GLC (eg 20% squalane on Chromosorb W-HMDS) for analytical characterization. The identification of the perfluorodimethylmorpholine derivatives can be carried out by means of MS, ¹⁹ F-NMR and elemental analysis.

Ausfuhrungsbeispiei

The invention will be explained in more detail by examples.

example 1

98 g (0.5 mol) of 4-cyclohexyl-2,6-dimethylmorpholine are dissolved in 0.61% anhydrous hydrogen fluoride and nickel anodes (4.4 dm ² ) in a Teflon cell at 5-8 V and O'C to 5 ° C elektrofluorieri. The electrofluorination was stopped after 150 h, the cell contents were transferred to a separating vessel and the lower phase separated. The separated perfluorocarbon phase was neutralized with aqueous sodium bicaronate solution, washed with water and coarsely distilled. The crude distillate was treated with 100 ml of 8 M KOH and 100 ml of dibutylamine and refluxed for 2 days, after which the perfluorocarbon was separated off and the treatment was repeated with lye and amine. Then, the perfluorocarbon was washed with dilute sulfuric acid, bicarbonate and water and distilled to give the over at 150-155 ⁰ C fraction was collected separately (37g). After purification by preparative GLC (20% Fomblin 425 on Chromosorb PAW), the compound was confirmed by MS and ' ⁹ F-NMR to be perfluoromycyclohexyl-β-dimethylmorpholine (yield 12%).

Claims (1)

1. A process for the preparation of perfluorinated N-substituted dimethylmorpholines of the general formula I. wherein A _{r is} a perfluoroalkyl radical having 2 to 8 carbon atoms or a 5- to 7-membered perfluorinated ring, wherein in each case in the chain or in the ring, a carbon atom may also be replaced by, an oxygen atom or by a perfluoroalkylamino group, and Bp is trifluoromethyl , characterized in that N-substituted dimethylmorpholines of the general formula II